Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25‐dihydroxy vitamin D3 (1,25‐(OH)2D3)
Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25‐dihydroxy vitamin D3 (1,25‐(OH)2D3)
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DOI：
10.1002/hipo.20908
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发表时间：
2012-03
期刊：
影响因子：
3.5
通讯作者：
Ying Zhu;Rong Zhou;Rong Yang;Zhuo Zhang;Yinyang Bai;Fei Chang;Lin Li;M. Sokabe;D. Goltzman;D. Miao;Ling Chen
中科院分区：
文献类型：
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作者：
Ying Zhu;Rong Zhou;Rong Yang;Zhuo Zhang;Yinyang Bai;Fei Chang;Lin Li;M. Sokabe;D. Goltzman;D. Miao;Ling Chen
本研究采用1α-羟化酶基因敲除（1α-（OH）ase−/−）小鼠，探讨1，25-二羟基维生素D3（1，25-（OH）2D 3）缺乏对成年海马齿状回（DG）神经发生的影响。与野生型同窝小鼠相比，8周龄1α-（OH）ase−/−小鼠中24 h-龄BrdU+细胞和增殖细胞核抗原阳性细胞的数量均增加约两倍。相比之下，与野生型小鼠相比，1α-（OH）ase−/−小鼠中7天和28天大的BrdU+细胞数量减少了50%，而BrdU+群体中BrdU+/NeuN+细胞的比例在1α-（OH）ase−/−和野生型小鼠之间没有差异。在1α-（OH）ase−/−小鼠中，DG颗粒下区（SGZ）的凋亡细胞显著增加。补充1，25-（OH）2D 3，但不纠正血清钙和磷水平，完全阻止了1α-（OH）ase−/−小鼠神经发生的变化。缺乏1，25-（OH）2D 3导致L型电压门控钙通道（L-VGCC）表达增加和神经生长因子（NGF）mRNA水平降低。用L-VGCC抑制剂硝苯地平治疗阻断了1，25-（OH）2D 3缺乏引起的细胞增殖增加。给予NGF显著减弱了1α-（OH）ase−/−小鼠新生神经元的丢失。© 2010 Wiley Periodicals，Inc.
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.