Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada.
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto M5G 1A8, Canada.
Stem Cell Reports. 2018 May 8;10(5):1464-1480. doi: 10.1016/j.stemcr.2018.03.008. Epub 2018 Apr 5.
Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools.
循环系统因子可以调节成体神经干细胞（NSC）的生物学特性，但这些循环信号的身份仍在确定之中。在这里，我们关注细胞因子白细胞介素-6（IL-6），因为循环中 IL-6 水平的升高与自闭症和双相情感障碍等神经病理有关。我们发现 IL-6 促进了产后鼠前脑 NSCs 的增殖，并且当 IL-6 受体在产后或成年神经前体细胞中可诱导敲除时，这会导致前脑 NSCs 的长期减少。此外，围产期或成年小鼠中 IL-6 的短暂循环激增会导致神经前体细胞增殖的急性增加，随后是成年 NSC 池的长期耗竭。因此，IL-6 信号对于成体 NSC 的自我更新是必要且充分的，并且在许多病理情况下观察到的循环 IL-6 的急性波动对成体 NSC 池的大小有持久的影响。
