Maternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon

Schizophrenia is a neurodevelopment disorder that is strongly associated with alterations in dopamine neurotransmission. Common features of animal models of schizophrenia include behavioural, cognitive and/or pharmacological abnormalities reflective of aberrant DA signaling. The aim of this study was to examine the expression of genes important for dopaminergic development and maturation within the embryonic mesencephalon using an epidemiologically-informed animal model of schizophrenia, the developmental vitamin D (DVD) deficient rat model. Two groups of female Sprague–Dawley rats were fed either a diet replete (1000 IU/kg) or deplete (0 IU/kg) of vitamin D, mated and foetal mesencephalon collected at embryonic day (E) E12 or E15. Using real time-PCR, the DVD-deficient embryos had a significant reduction in factors crucial in specifying dopaminergic phenotype, such as Nurr1 and p57Kip2. No group differences were found for Lmx1b or Ptx3. Reductions in these specification factors may alter the ontogeny of DA neurons and may ultimately help to explain the behavioural abnormalities reported in adult offspring from this model.

Research highlights▶ Developmental vitamin D deficiency reduces crucial specification genes for dopamine, Nurr1 and p57kip2. ▶ Reduction in these genes may lead to alterations in dopamine neuron maturation and function. ▶ A reduction in these genes early in development may be responsible for behavioural phenotypes in DVD-deficient adult.