P-BN005. Maternal vitamin B12 deficiency is associated with increased oxidative stress and DNA damage in brain regions of C57BL/6 mouse offspring

Abstract

Introduction . Maternal micronutrient deficiencies are predominant in developing countries. Vitamin B12 deficiency is common in women, especially during child-bearing age. Maternal vitamin B12 deficiency is known to have a profound impact on the developing fetus and programs it to a number of complex adult-onset disorders like cardiovascular diseases, diabetes, neurological disturbances, etc. We hypothesized that increased oxidative stress and reduced activity of antioxidant enzymes along with DNA damage in the brain are associated with the etiology of these complications. As little is known about the effects of maternal vitamin B12 restriction on brain regions of the offspring, we have focused particularly on the cerebral cortex and hippocampus in our study. Methods . Female, weaning C57BL/6 mice received ad libitum for 4 weeks a control diet (American Institute of Nutrition-76A) or the same with restriction of vitamin B12. After confirming the deficiency, the mice were allowed to breed with control males to obtain the F1 generation offspring. The different parameters related to oxidative stress and DNA damage were assessed at 3 months of age of the offspring. Results . Interestingly, offspring born to mice fed on vitamin B12 restricted diet had a significantly higher degree of oxidative stress in both the cerebral cortex and hippocampus as reflected by their increased levels of lipid peroxidation and protein oxidation. Also, the activity of antioxidant enzymes (superoxide dismutase and catalase) was diminished in both the brain regions of offspring born to mice fed on vitamin B12 restricted diet. DNA damage in the form of single and double-stranded DNA breaks were also increased in the cerebral cortex and hippocampus of mice offspring born to vitamin B12 restricted dams. Conclusion . To conclude, maternal vitamin B12 deficiency is associated with increased oxidative stress in the brain of young offspring, which further leads to DNA damage in the brain.