Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25‐dihydroxy vitamin D3 (1,25‐(OH)2D3)

In this study, we employed 1α‐hydroxylase knockout (1α‐(OH)ase−/−) mice to investigate the influence of 1,25‐dihydroxy vitamin D3 (1,25‐(OH)2D3) deficiency on the adult neurogenesis in the hippocampal dentate gyrus (DG). The numbers of both 24‐hr‐old BrdU+ cells and proliferating cell nuclear antigen positive cells in 8‐week‐old 1α‐(OH)ase−/− mice increased approximately twofold compared with wild‐type littermates. In contrast, the numbers of 7‐ and 28‐day‐old BrdU+ cells in 1α‐(OH)ase−/− mice decreased by 50% compared with wild‐type mice, while the proportion of BrdU+/NeuN+ cells in BrdU+ population showed no difference between 1α‐(OH)ase−/− and wild‐type mice. Apoptotic cells in the subgranular zone (SGZ) of DG markedly increased in 1α‐(OH)ase−/− mice. Replenishment of 1,25‐(OH)2D3, but not correction of serum calcium and phosphorus levels, completely prevented changes in the neurogenesis in 1α‐(OH)ase−/− mice. The absence of 1,25‐(OH)2D3 led to an increase in the expression of L‐type voltage‐gated calcium channel (L‐VGCC) and a decrease in the nerve growth factor (NGF) mRNA level. Treatment with the L‐VGCC inhibitor nifedipine blocked the increased cell proliferations by 1,25‐(OH)2D3 deficiency. Administration of NGF significantly attenuated the loss of newborn neurons in 1α‐(OH)ase−/− mice. © 2010 Wiley Periodicals, Inc.