State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
CNS Neurosci Ther. 2013 Sep;19(9):705-13. doi: 10.1111/cns.12129. Epub 2013 Jun 7.
This study investigated the influence of sigma-1 receptor (σ1 R) deficiency on adult neurogenesis.
We employed 8-week-old male σ1 R knockout (σ1 R(-/-) ) mice to examine the proliferation and differentiation of progenitor cells, and the survival and neurite growth of newborn neurons in hippocampal dentate gyrus (DG).
In comparison with wild-type (WT) littermates, the numbers of 24-h-old BrdU(+) cells and Ki67(+) cells in σ1 R(-/-) mice increased, while the number of 28-day-old BrdU(+) cells decreased without changes in proportion of BrdU(+) /NeuN(+) cells and BrdU(+) /GFAP(+) cells. The neurite density of newborn neurons was slightly reduced in σ1 R(-/-) mice. In DG granular cells, N-methyl-d-aspartate (NMDA)-activated current (INMDA ) and phosphorylation of NMDA receptor (NMDAr) NR2B were reduced in σ1 R(-/-) mice without the alteration of NR2B expression and membrane properties compared to WT mice. The NR2B antagonist abolished the difference in INMDA between σ1 R(-/-) mice and WT mice. The application of NMDAr agonist in σ1 R(-/-) mice prevented the over-proliferation of cells and reduction in newborn neurons, but it had no effects on the hypoplastic neurite. The administration of NMDAr antagonist in WT mice enhanced the cell proliferation and depressed the survival of newborn neurons.
The σ1 R deficiency impairs neurogenesis in DG through down-regulation of NMDArs.
本研究旨在探讨 sigma-1 受体（σ1 R）缺失对成年神经发生的影响。
我们使用 8 周龄雄性 σ1 R 敲除（σ1 R(-/-)）小鼠，以检测祖细胞的增殖和分化，以及海马齿状回（DG）中新生神经元的存活和突起生长。
与野生型（WT）同窝仔相比，σ1 R(-/-) 小鼠 24 小时龄 BrdU(+) 细胞和 Ki67(+) 细胞数量增加，而 28 天龄 BrdU(+) 细胞数量减少，但 BrdU(+) /NeuN(+) 细胞和 BrdU(+) /GFAP(+) 细胞的比例没有变化。新生神经元的突起密度在 σ1 R(-/-) 小鼠中略有降低。在 DG 颗粒细胞中，与 WT 小鼠相比，N-甲基-D-天冬氨酸（NMDA）激活电流（INMDA）和 NMDA 受体（NMDAr）NR2B 磷酸化减少，而 NR2B 表达和膜特性没有改变。NR2B 拮抗剂消除了 σ1 R(-/-) 小鼠和 WT 小鼠之间 INMDA 的差异。NMDA 受体激动剂在 σ1 R(-/-) 小鼠中的应用可防止细胞过度增殖和新生神经元减少，但对发育不良的突起没有影响。NMDA 受体拮抗剂在 WT 小鼠中的给药增强了细胞增殖并抑制了新生神经元的存活。
σ1 R 缺失通过下调 NMDArs 损害 DG 中的神经发生。
