Background: Animal studies and in vitro experiments indicate that vitamin D is involved in a diverse range of neurobiological functions. We had the opportunity to examine the relationship between serum 25-hydroxyvitamin D₃ [25(OH)D] levels and performance on various cognitive tasks, based on a large, representative community sample. Methods: Three age groups were available from the population-based NHANES III survey: adolescent group (n = 1,676, age range 12–17 years), adult group (n = 4,747, 20–60 years), elderly group (n = 4,809, 60–90 years). The associations between eight psychometric measures and serum 25(OH)D were assessed. Results: In the adolescent and adult groups, none of the psychometric measures were associated with 25(OH)D levels. In the elderly group there was a significant difference between 25(OH)D quintiles performance on a learning and memory task; however, those with the highest quintile of 25(OH)D were most impaired on the task, contrary to the hypotheses. Conclusion: Lower 25(OH)D levels were not associated with impaired performance on various psychometric measures. While it remains to be seen if chronic exposure to low 25(OH)D levels alters brain function in the long term, this cross-sectional study suggests that 25(OH)D levels do not influence neurocognitive performance.

There is growing evidence for a role of vitamin D3 signalling in the brain. In this study, we investigated the influence of vitamin D3, in combination with glucocorticoids, on differentiation of the hippocampal progenitor line HIB5, as well as survival of rat primary hippocampal cells. In HIB5, pre-treatment with dexamethasone (Dex) alone inhibited neurite outgrowth and abolished activation of the mitogen-activated protein kinase (MAPK) pathway during platelet-derived growth factor (PDGF)-induced differentiation, consistent with previous findings. Interestingly, pre-treating HIB5 with vitamin D3 significantly reduced these effects of Dex and, in addition, lowered the transactivational function of the glucocorticoid receptor (GR) in transient reporter gene assays. A further impact of vitamin D3 on glucocorticoid effects was observed in a rat primary hippocampal culture known to be particularly sensitive to prolonged GR activation. In this model, Dex induced considerable cell death after 72 h of exposure in vitro. However, 24 h of pre-treatment with low doses of vitamin D3 substantially reduced the degree of Dex-induced apoptosis in primary hippocampal cells. Taken together, our experiments demonstrate a cross-talk between vitamin D3 and glucocorticoids in two hippocampal models, a feature that may have important implications in disorders with dysregulated glucocorticoid signalling, including major depression.

Mineralocorticoid (MR) and glucocorticoid (GR) receptors are two closely-related members of the steroid nuclear receptor family of transcription factors that bind common ligands in the brain (corticosterone and cortisol) and supposedly have identical hormone response elements. This raises the important question of how they can elicit differential biological actions in neurons in which they are often colocalized. One plausible explanation is that they differentially recruit proteins (coregulators or other receptor-interacting factors) through cell-specific interactions with regions that diverge between MR and GR to modulate target gene transcription in a receptor-specific manner. We therefore performed a yeast-two-hybrid screening of a human brain cDNA library with an AF1-containing region of the human MR as bait. This screening revealed several potential MR-interacting partners; among them were several clones bearing homology to DAXX, FLASH, and FAF-1, all previously implicated in apoptosis. Coexpression of candidate clones in a mouse hippocampal cell line confirmed these interactions in a mammalian neural cell environment as well. In transient transactivation assays, DAXX and FLASH influenced MR-and GRdriven transcription of the MMTV-Luc reporter similarly; in contrast, although FAF-1 did not transactivate GR, it did selectively stimulate MR-mediated transcription. Thus, the present findings, that 1) DAXX, FLASH, and FAF-1 modulate the transcriptional activities of MR and GR and that 2) FAF-1 selectively coactivates only MR, provide possible clues for how these closely related receptors might differentially influence neuronal function.

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In this study we evaluated the possible protective effects of selenium (Se) on hematological and oxidative stress parameters in rats chronically treated with cisplatin (cisPt). Four groups of Wistar albino rats were examined: a control, untreated rats (I), rats treated with Se (II), rats treated with cisPt (III), and rats treated with Se and cisPt (IV). All animals were treated for 5 days successively and killed 24 h after the last treatment. Hematological and oxidative stress parameters were followed in whole blood and red blood cells (RBC). Results showed that the chronic application of Se was followed by a higher number of reticulocytes and platelets, increased lipid peroxidation and GSH content in the RBC. Cisplatin treatment induced depletion of RBC and platelet numbers and an elevation of the superoxide anion, nitrites and glutathione levels. Se and cisPt co-treatment was followed by an elevation of the hematological parameters and the recovery of the glutathione status when compared to the control and cisPt-treated rats