Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine

Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate d...

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Vydané v:	The Journal of nutrition Ročník 138; číslo 12; s. 2502
Hlavní autori:	Troen, Aron M, Chao, Wei-Hsun, Crivello, Natalia A, D'Anci, Kristen E, Shukitt-Hale, Barbara, Smith, Don E, Selhub, Jacob, Rosenberg, Irwin H
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.12.2008
Predmet:	Animals Brain - metabolism Cognition Disorders - blood Cognition Disorders - etiology Cognition Disorders - metabolism Cognition Disorders - prevention & control Dietary Supplements Folic Acid Deficiency - complications Folic Acid Deficiency - diet therapy Folic Acid Deficiency - metabolism Folic Acid Deficiency - psychology Homocystine - blood Lecithins - metabolism Male Maze Learning Methionine - administration & dosage Psychomotor Performance Rats Rats, Sprague-Dawley S-Adenosylhomocysteine - metabolism S-Adenosylmethionine - metabolism
ISSN:	1541-6100, 1541-6100
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Abstract	Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction.
AbstractList	Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction. Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction.Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction.
Author	Crivello, Natalia A Shukitt-Hale, Barbara Smith, Don E D'Anci, Kristen E Selhub, Jacob Chao, Wei-Hsun Troen, Aron M Rosenberg, Irwin H
Author_xml	– sequence: 1 givenname: Aron M surname: Troen fullname: Troen, Aron M email: aron.troen@tufts.edu organization: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. aron.troen@tufts.edu – sequence: 2 givenname: Wei-Hsun surname: Chao fullname: Chao, Wei-Hsun – sequence: 3 givenname: Natalia A surname: Crivello fullname: Crivello, Natalia A – sequence: 4 givenname: Kristen E surname: D'Anci fullname: D'Anci, Kristen E – sequence: 5 givenname: Barbara surname: Shukitt-Hale fullname: Shukitt-Hale, Barbara – sequence: 6 givenname: Don E surname: Smith fullname: Smith, Don E – sequence: 7 givenname: Jacob surname: Selhub fullname: Selhub, Jacob – sequence: 8 givenname: Irwin H surname: Rosenberg fullname: Rosenberg, Irwin H
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SubjectTerms	Animals Brain - metabolism Cognition Disorders - blood Cognition Disorders - etiology Cognition Disorders - metabolism Cognition Disorders - prevention & control Dietary Supplements Folic Acid Deficiency - complications Folic Acid Deficiency - diet therapy Folic Acid Deficiency - metabolism Folic Acid Deficiency - psychology Homocystine - blood Lecithins - metabolism Male Maze Learning Methionine - administration & dosage Psychomotor Performance Rats Rats, Sprague-Dawley S-Adenosylhomocysteine - metabolism S-Adenosylmethionine - metabolism
Title	Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine
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