Transient prenatal and early life hypovitaminosis D induce permanent alterations in brain morphology, cell density and gene expression consistent with alterations observed in schizophrenia
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Background: Based on data from ecological and analytic epidemiological studies, we have proposed that low prenatal vitamin D is a candidate risk-modifying factor for schizophrenia. Previously, we demonstrated that low prenatal vitamin D adversely affected brain development in neonatal rats (Eyles et al., 2003, Neuroscience, 118(3): 641-53). Methods: Here, we examine the impact of both prenatal and early life hypovitaminosis D on various outcomes in the adult rat brain. We compared the brains of adult offspring from control vs. vitamin D deplete dams who were either repleted with vitamin D (a) at birth or (b) at weaning. Results: In the offspring of depleted dams, we found a significant persistent dose-related increase in lateral ventricle volume and alterations in anterior cingulate and prefrontal cortical cell densities (consistent with the known prodifferentiation properties of this steroid). We also observed a reduced expression of NGF as well as a down-regulation of transcripts coding for GABAA alpha 4 receptor, MAP2 and Neurofilament L in the deplete group. An increase in prefrontal cortical cell density and a reduction in MAP2 and neurofilament (and therefore presumably neuronal architecture) are all in accordance with the proposal that schizophrenia is a disease of reduced connectivity/neuropil. Conclusion: These findings provide further evidence that vitamin D is involved in brain development. Moreover, the persistent ventriculomegaly and apparent reduction in the expression of structural neuronal transcripts confirms the biological plausibility of early life hypovitaminosis D as a risk factor for schizophrenia.
12th Biennial Winter Workshop on Schizophrenia. Abstracts (Schizophrenia Research)
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HISTORY AND ARCHAEOLOGY