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

In this study, we employed 1a-hydroxylase knockout (1a-(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 1a-(OH)ase-/- mice increased approximately twofold compared with wild-type littermates. In contrast, the numbers of 7- and 28-day-old BrdU+ cells in 1a-(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 1a-(OH)ase-/- and wild-type mice. Apoptotic cells in the subgranular zone (SGZ) of DG markedly increased in 1a-(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 1a-(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 1a-(OH)ase-/- mice. (c) 2010 Wiley Periodicals, Inc.