University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland.
Department of Biomedicine, University of Basel, Basel, 4056, Switzerland.
Nat Commun. 2019 Sep 4;10(1):3983. doi: 10.1038/s41467-019-11870-x.
Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.
缺氧缺血（HI）是一种发生在所有年龄段的急性脑威胁。治疗性低温可以改善新生儿的损伤，但它的副作用阻止了在成人中的常规使用。低温上调了一小部分蛋白质，包括 RNA 结合基序蛋白 3（RBM3），在应激条件下具有神经保护作用。在这里，我们展示了 RBM3 如何刺激神经元分化并抑制持续成人神经发生的两个区域（SVZ 和 SGZ）中的 HI 诱导的细胞凋亡，同时仅在 SGZ 中促进 HI 损伤后的神经干细胞/祖细胞（NSPC）增殖。RBM3 与 IGF2 mRNA 结合蛋白 2（IMP2）相互作用，提高其表达，从而刺激 SGZ 中的 IGF2 释放，但不刺激 SVZ-NSPC 中的 IGF2 释放。总之，我们描述了通过新的 RBM3-IMP2-IGF2 信号通路，在成人 HI 损伤后，神经发生的依赖于小生境的调节。
