There is growing evidence that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 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, our group has explored the role of 1,25(OH)2D3 in brain development 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 15-23, and 1,25(OH)2D3 induces the expression of nerve growth factor and stimulates neurite outgrowth in embryonic hippocampal explant cultures. In the neonatal rat, low prenatal vitamin D3 in utero leads to increased brain size, altered brain shape, enlarged ventricles, reduced expression of nerve growth factors, reduced expression of the low affinity p75 receptor and increased cellular proliferation. In summary, there is growing evidence that low prenatal levels of 1,25(OH)2D3 can influence critical components of orderly brain development. It remains to be seen if these processes are of clinical relevance in humans, but in light of the high rates of hypovitaminosis D in pregnant women and neonates, this area warrants further scrutiny. © 2004 Elsevier Ltd. All rights reserved.
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