Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
Neuron. 2018 Oct 10;100(1):183-200.e8. doi: 10.1016/j.neuron.2018.08.030. Epub 2018 Sep 27.
Acute infection, if not kept in check, can lead to systemic inflammatory responses in the brain. Here, we show that within 2 hr of systemic inflammation, PDGFRβ mural cells of blood vessels rapidly secrete chemokine CCL2, which in turn increases total neuronal excitability by promoting excitatory synaptic transmission in glutamatergic neurons of multiple brain regions. By single-cell RNA sequencing, we identified Col1a1 and Rgs5 subgroups of PDGFRβ cells as the main source of CCL2. Lipopolysaccharide (LPS)- or Poly(I:C)-treated pericyte culture medium induced similar effects in a CCL2-dependent manner. Importantly, in Pdgfrb-Cre;Ccl2 mice, LPS-induced increase in excitatory synaptic transmission was significantly attenuated. These results demonstrate in vivo that PDGFRβ cells function as initial sensors of external insults by secreting CCL2, which relays the signal to the central nervous system. Through their gateway position in the brain, PDGFRβ cells are ideally positioned to respond rapidly to environmental changes and to coordinate responses.
急性感染如果得不到控制，可能会导致大脑出现全身炎症反应。在这里，我们发现全身炎症发生后 2 小时内，血管 PDGFRβ 壁细胞迅速分泌趋化因子 CCL2，进而通过促进多个脑区谷氨酸能神经元的兴奋性突触传递，增加神经元整体的兴奋性。通过单细胞 RNA 测序，我们确定 Col1a1 和 Rgs5 亚群 PDGFRβ 细胞是 CCL2 的主要来源。脂多糖 (LPS) 或 Poly(I:C) 处理的周细胞培养物以 CCL2 依赖的方式诱导类似的效果。重要的是，在 Pdgfrb-Cre;Ccl2 小鼠中，LPS 诱导的兴奋性突触传递增加明显减弱。这些结果表明，PDGFRβ 细胞通过分泌 CCL2 作为外部刺激的初始传感器，将信号传递到中枢神经系统。PDGFRβ 细胞位于大脑的“门户”位置，非常适合对环境变化做出快速反应并协调反应。
