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Introduction: Vitamin B 12 deficiency presents various neurological manifestations, such as cognitive dysfunction, mental retardation, or memory impairment. However, the involved molecular mechanisms remain to date unclear. Vitamin B 12 is essential for synthesizing S-adenosyl methionine (SAM), the methyl group donor used for almost all transmethylation reactions. Here, we investigate the m6A methylation of mRNAs and their related gene expression in models of vitamin B 12 deficiency., Methods and Results: This study observes two cellular models deficient in vitamin B 12 and hippocampi of mice knock-out for the CD320 receptor. The decrease in SAM levels resulting from vitamin B 12 deficiency is associated with m 6 A reduced levels in mRNAs. This is also potentially mediated by the overexpression of the eraser FTO. We further investigate mRNA methylation of some genes involved in neurological functions targeted by the m6A reader YTH proteins. We notably observe a m6A hypermethylation of Prkca mRNA and a consistently increased expression of PKCα, a kinase involved in brain development and neuroplasticity, in the two cellular models., Conclusion: Our data show that m6A methylation in mRNA could be one of the contributing mechanisms that underlie the neurological manifestations produced by vitamin B 12 deficiency., (© 2021 Wiley-VCH GmbH.)

Scope: Vitamin B12 and folate (methyl donors) deficiency is frequent during pregnancy. Experimental rat models with methyl donor deficit during pregnancy and lactation (Initial methyl donor deficit (iMDD)) produce impaired myocardium fatty acid oxidation and mitochondrial energy metabolism at weaning., Methods and Results: The consequences of iMDD on heart of rat pups under normal diet after weaning and high fat diet (HF) between day (D) 50 and D185 are investigated. iMDD/HF induces increased histological fibrosis and increased B-type natriuretic peptide blood level. Inflammation is evidenced by increased protein expression of NFkB, Caspase1, and IL1β and fibrosis by increased expression of αSMA, col1a1, and col1a2 in females, but not in males. Fibrosis is related to increased angiotensin at D50 and D185 and increased protein expression of TGFB1 and AT1 angiotensin receptors at D185. The limited fibrosis in males is consistent with increased expression of AT2, the antagonist receptor of AT1. The increased expression of GLUT4 and decreased expression of PGC1α and PPARα reflect a shift from fatty acid oxidation to glycolysis., Conclusion: Developmental programming by iMDD produces cardiomyopathy in female offspring exposed to HF. The cardiomyopathy is linked to inflammation and fibrosis through angiotensin-AT2 and TGFB1 pathways and alteration of energy metabolism., (© 2021 Wiley-VCH GmbH.)