Department of Pharmacology, Physiology and Neuroscience, Rutgers Biomedical Health Sciences of Rutgers University, 205 South Orange Ave. Newark, NJ 07103, USA.
ICON Laboratory Services, Farmingdale, NY 11735, USA.
Stem Cell Reports. 2020 May 12;14(5):861-875. doi: 10.1016/j.stemcr.2020.03.019. Epub 2020 Apr 16.
Interleukin-6 (IL-6) is increased in maternal serum and amniotic fluid of children subsequently diagnosed with autism spectrum disorders. However, it is not clear how increased IL-6 alters brain development. Here, we show that IL-6 increases the prevalence of a specific platelet-derived growth factor (PDGF)-responsive multipotent progenitor, with opposite effects on neural stem cells and on subsets of bipotential glial progenitors. Acutely, increasing circulating IL-6 levels 2-fold above baseline in neonatal mice specifically stimulated the proliferation of a PDGF-responsive multipotential progenitor accompanied by increased phosphorylated STAT3, increased Fbxo15 expression, and decreased Dnmt1 and Tlx expression. Fate mapping studies using a Nestin-CreERT2 driver revealed decreased astrogliogenesis in the frontal cortex. IL-6-treated mice were hyposmic; however, olfactory bulb neuronogenesis was unaffected. Altogether, these studies provide important insights into how inflammation alters neural stem cells and progenitors and provide new insights into the molecular and cellular underpinnings of neurodevelopmental disorders associated with maternal infections.
白细胞介素-6（IL-6）在随后被诊断患有自闭症谱系障碍的儿童的母血清和羊水中增加。然而，增加的 IL-6 如何改变大脑发育尚不清楚。在这里，我们表明 IL-6 增加了特定血小板衍生生长因子（PDGF）反应性多能祖细胞的患病率，对神经干细胞和双潜能神经胶质祖细胞亚群产生相反的影响。急性地，在新生小鼠中使循环中的 IL-6 水平升高至基线以上 2 倍，特异性地刺激了 PDGF 反应性多能祖细胞的增殖，伴随着磷酸化 STAT3 的增加、Fbxo15 表达的增加以及 Dnmt1 和 Tlx 表达的减少。使用 Nestin-CreERT2 驱动子进行的命运图谱研究表明，在前额叶皮层中星形胶质发生减少。IL-6 处理的小鼠嗅觉迟钝；然而，嗅球神经元发生不受影响。总的来说，这些研究为炎症如何改变神经干细胞和祖细胞提供了重要的见解，并为与母体感染相关的神经发育障碍的分子和细胞基础提供了新的见解。
