Prepubertal continuous dietary folate fortification enhances brain function of adult mice by modulating antioxidant status, inflammation and brain neurotransmitter levels

Abstract

Abstract Background There is a growing body of knowledge in support of the beneficial effects of folic acid supplementation. However, while ample evidence exists concerning beneficial effects on growth and haematologic parameters, possible effects of continuous folic acid supplementation on the brain are less examined. Objectives To investigate possible effect of dietary folic acid supplementation (beginning in the prepubertal period) on neurobehaviour, oxidative stress, inflammatory parameters and neurotransmitter levels in adult mice. Methods Forty-eight prepubertal male mice (postnatal day 21) were randomly assigned into four groups of 12 (n = 12) animals each. Mice were grouped into normal control (fed standard diet) and three groups fed folic acid supplemented diet at 2.5, 5 and 10 mg/kg of feed. Daily food intake and weekly body weight were assessed. Animals were fed standard diet, or folic acid supplemented diet for a period of eight weeks. On postnatal day 78, animals were exposed to behavioural paradigms (Open-field, Y maze, radial arm maze, elevated plus maze, bar test and models of behavioural despair). Twenty-four hours after the last behavioural test, animals were fasted overnight following which they were sacrificed, and blood taken for assessment of blood glucose, leptin, and insulin levels. The brain of the animals were also homogenised for the assessment of biochemical parameters (lipid peroxidation, total antioxidant capacity, inflammatory markers, dopamine, brain derived neurotropic factor, acetylcholine and acetylcholinesterase activity). Results Results showed a concentration dependent increase/improvement in body weight, antioxidant status, memory scores (in the radial arm and Y- maze) and acetylcholine levels; and a decrease in food intake, blood glucose, insulin, and leptin level. A reduction in open field behaviours, anxiety-related behaviours, and proinflammatory markers were also observed. Conclusion The beneficial effects of prepubertal continuous dietary folate fortification in specific contexts relating to behaviour, cognition, oxidative status, metabolic hormones and brain neurochemistry (as the animal ages) are shown in the study.