Converging evidence from human and animal studies support an association between vitaminDdeficiency and cognitive impairment. Previous studies have shown that hippocampal volume is reduced in adults with vitaminDdeficiency as well as in a range of disorders, such as schizophrenia.
The aim of the current study was to examine the effect of adultvitaminD (AVD) deficiency on hippocampal-dependentspatial learning, and hippocampal volume and connectivity in healthy adultmice. Ten-week-old male BALB/cmice were fed a control (vitaminD 1500 IU/kg) or vitaminD-depleted (vitaminD 0 IU/kg) diet for a minimum of 10 weeks. The mice were then tested for hippocampal-dependent spatial learning using active place avoidance (APA) and on tests of muscle and motor coordination (rotarod and grip strength). The mice were perfused and brains collected to acquire ex vivo structural and diffusion-weighted images using a 16.4 T MRI scanner. We also performed immunohistochemistry to quantify perineuronal nets (PNNs) and parvalbumin (PV) interneurons in various brain regions. AVD-deficient mice had a lower latency to enter the shock zone on APA, compared to control mice, suggesting impaired hippocampal-dependent spatial learning.
There were no differences in rotarod or grip strength, indicating that AVD deficiency did not have an impact on muscle or motor coordination. AVD deficiency did not have an impact on hippocampal volume. However, AVD-deficient mice displayed a disrupted network centred on the right hippocampus with abnormal connectomes among 29 nodes. We found a reduction in PNN positive cells, but no change in PV, centred on the hippocampus.
Our results provide compelling evidence to show that AVD deficiency in otherwise healthy adultmice may play a key role in hippocampal-dependentlearning and memory formation. We suggest that the spatial learningdeficits could be due to the disruption of right hippocampal structuralconnectivity.
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