Skip to Content
Merck
  • Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet.

Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet.

Neurobiology of disease (2014-10-07)
Ethika Tyagi, Yumei Zhuang, Rahul Agrawal, Zhe Ying, Fernando Gomez-Pinilla
ABSTRACT

Quality nutrition during the period of brain formation is a predictor of brain functional capacity and plasticity during adulthood; however it is not clear how this conferred plasticity imparts long-term neural resilience. Here we report that early exposure to dietary omega-3 fatty acids orchestrates key interactions between metabolic signals and Bdnf methylation creating a reservoir of neuroplasticity that can protect the brain against the deleterious effects of switching to a Western diet (WD). We observed that the switch to a WD increased Bdnf methylation specific to exon IV, in proportion to anxiety-like behavior, in Sprague Dawley rats reared in low omega-3 fatty acid diet, and these effects were abolished by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Blocking methylation also counteracted the reducing action of WD on the transcription regulator CTCF binding to Bdnf promoter IV. In vitro studies confirmed that CTCF binding to Bdnf promoter IV is essential for the action of DHA on BDNF regulation. Diet is also intrinsically associated to cell metabolism, and here we show that the switch to WD downregulated cell metabolism (NAD/NADH ratio and SIRT1). The fact that DNA methyltransferase inhibitor did not alter these parameters suggests they occur upstream to methylation. In turn, the methylation inhibitor counteracted the action of WD on PGC-1α, a mitochondrial transcription co-activator and BDNF regulator, suggesting that PGC-1α is an effector of Bdnf methylation. Results support a model in which diet can build an "epigenetic memory" during brain formation that confers resilience to metabolic perturbations occurring in adulthood.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tris(tert-butoxy)silanol, 99.999%
Sigma-Aldrich
Benzethonium chloride, BioUltra, ≥99.0% (AT)
Sigma-Aldrich
Benzethonium chloride, ≥97% (titration), ≥98% (HPLC)
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥98.5% (GC)
Sigma-Aldrich
Glycerol solution, puriss., meets analytical specification of Ph. Eur., BP, 84-88%
Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥99.0% (T)
Sigma-Aldrich
Anti-MeCP2 Antibody, Upstate®, from rabbit
Benzethonium chloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Benzethonium Chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Anti-CTCF Antibody, serum, Upstate®
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, ≥95% (HPLC)
Sigma-Aldrich
(L)-Dehydroascorbic acid
Sigma-Aldrich
Dehydro-L-(+)-ascorbic acid dimer, ≥80% (enzymatic)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide lithium salt from Saccharomyces cerevisiae, ≥95%
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, ≥99%
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, purified by column chromatography, ≥99%
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, Grade AA-1
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide, pkg of 10 mg (per vial)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide, pkg of 20 mg (per vial)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide, pkg of 50 mg (per vial)
Sigma-Aldrich
Glycerol, ACS reagent, ≥99.5%
Sigma-Aldrich
Glycerol, SAJ first grade, ≥98.0%
USP
Glycerin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Glycerol, ReagentPlus®, ≥99.0% (GC)
Sigma-Aldrich
Glycerol, ≥99.5%
Sigma-Aldrich
Glycerol, FCC, FG
Sigma-Aldrich
Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)