Figure 8.

Schematic model for Neat1/Hbb axis regulating post-sepsis cognitive impairment

During sepsis, neurons are exposed to hypoxic environments, which results in upregulation of Neat1 levels. Neat1 directly interacts with Hbb and stabilizes its protein levels via inhibiting Hbb ubiquitination. Furthermore, Hbb suppression of PSD-95 expression results in decreased dendritic spine density, which is critical for cognition and memory. In addition, suppression of Neat1 via GapmeR promotes degradation of Hbb, resulting in increases of PSD-95 levels, reduction of synaptic dysfunction, and mitigation of cognitive impairment post-sepsis.