| First Author | Tan C | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 577 |
| Pages | 38-44 | PubMed ID | 34507063 |
| Mgi Jnum | J:339057 | Mgi Id | MGI:6788772 |
| Doi | 10.1016/j.bbrc.2021.09.003 | Citation | Tan C, et al. (2021) Deficiency of cGAS signaling protects against sepsis-associated encephalopathy. Biochem Biophys Res Commun 577:38-44 |
| abstractText | Sepsis is a life-threatening inflammatory syndrome secondary to infection. Thanks to the advances of antibiotics and life-supporting techniques, the mortality of sepsis has been decreasing in recent decades. Nevertheless, sepsis-associated encephalopathy (SAE) is still common in septic patients, which promotes the mortality of septic patients and results in cognitive dysfunction in survivors. Full understanding and effective medicine in the treatment of SAE is currently scant. Here, we revealed a novel role of cGAS signaling in the pathogenesis of SAE. Deficiency of cGas significantly restored cognitive impairment in sepsis mice model. The restoration may attribute to the recovery of neo-neuron decline that associated with the decrease of activated microglia and astrocytes in the hippocampus of cGas-deficient mice. In addition, type I interferon (IFN) signaling, a downstream of cGAS pathway, was boosted in the hippocampus of septic mice, which was dramatically attenuated by deleting cGas. Moreover, administration of recombinant IFNbeta markedly reversed the protection of ablation of cGas in the cognitive impairment in sepsis. Collectively, cGAS promotes the pathogenesis of SAE by up-regulating type I IFN signaling. Blocking cGAS may be a promising strategy for preventing encephalopathy in sepsis. |
