Changes in dietary folate intake differentially affect oxidised lipid and mitochondrial DNA damage in various brain regions of rats in the absence/presence of intracerebroventricularly injected amyloid β-peptide challenge

• Published in: British journal of nutrition 2011-05, Vol.105 (9), p.1294-1302
• Main Authors: Chen, Ta-Fu, Chiu, Ming-Jang, Huang, Chou-Tz, Tang, Ming-Chi, Wang, Sue-Jane, Wang, Chia-Chuan, Syu Huang, Rwei-Fen
• Format: Article
• Language: English
• Subjects: Alzheimer disease; amyloid; Amyloid beta-Peptides - administration & dosage; Animal Feed - analysis; Animals; Biological and medical sciences; Brain - cytology; Cell Death - drug effects; cortex; death; Diet; DNA damage; DNA Damage - drug effects; DNA, Mitochondrial - drug effects; Dose-Response Relationship, Drug; drinking water; Feeding. Feeding behavior; folic acid; Folic Acid - pharmacology; Fundamental and applied biological sciences. Psychology; genotoxicity; hippocampus; Infusions, Intraventricular; Lipid Peroxidation; Male; mitochondrial DNA; Molecular Nutrition; Neurons - drug effects; Rats; risk; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114510005052

Accumulating evidence suggests that changes in dietary folate intake may modulate the risks of Alzheimer's disease (AD) through as yet unknown mechanisms. The aims of the present study were to investigate how dietary folate affects the brain folate distribution, levels of oxidised lipid and DNA damage in the absence/presence of β-amyloid(25–35) (Aβ) peptide challenge, a pathogenic hallmark of AD. Male Wistar rats were assigned to diets with folic acid at 0 (folate deprivation; FD), 8 (moderate folate; MF) and 8 mg folic acid/kg diet+0·003 % in drinking-water (folate supplementation; FS) for 4 weeks. A single injection of Aβ peptide (1 mg/ml) or the vehicle solution was intracerebroventricularly (icv) administrated to rats a week before killing. Brain folate, a marker of oxidative injury, and neuronal death were assayed. In the absence of an Aβ injection, FD rats showed reduced folate levels, and increased 2-thiobarbituric acid-reactive substances and a mitochondrial (mt)DNA 4834 bp large deletion (mtDNA4834 deletion) in the hippocampus compared with the counterpart brains of control rats (P