Prenatal vitamin D deficiency and brain development

Abstract

There is growing evidence that vitamin D is active in the brain but until recently there was a lack of evidence about its role during brain development. Guided by certain features of the Epidemiology of schizophrenia, we have explored the role of vitamin D in the developing brain using whole animal models and in vitro culture studies. The expression of the vitamin D receptor (VDR) in the embryonic rat brain rises steadily between embryonic day 15 to day 23 and vitamin D induces the expression of nerve growth factor and stimulates neurite outgrowth in embryonic hippocampal explant cultures. In the pregnant rat, low maternal vitamin D alters the way the brain develops in the newborn offspring, leading to increased brain size, altered brain shape, enlarged ventricles, reduced expression of neurotrophic growth factors, reduced expression of the pan-neurotrophin receptor, p75NTR and increased cellular proliferation. The effects of prenatal vitamin D deficiency are long lasting because certain abnormalities in brain morphology persist and behavioural alterations are observed in the adult offspring, despite a return to normal vitamin D levels during postnatal life. These affects are specific to transient prenatal vitamin D depletion because adult vitamin D depletion, combined prenatal and chronic postnatal vitamin D depletion, or ablation of the vitamin D receptor in mice lead to markedly different outcomes. In summary, there is growing evidence that low prenatal levels of vitamin D can influence critical components of orderly brain development and that this has a long lasting effect on the adult brain.