Developmental Vitamin D3 deficiency alters the adult rat brain

There is growing evidence that Vitamin D3 (1,25-dihydroxyvitamin D3) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D3 deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D3 deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D3 deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D3 deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-Aα4. We conclude that transient early life hypovitaminosis D3 not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D3 in women of child-bearing age, the public health implications of these findings warrant attention.