Cecal slurry-induced sepsis in mice impairs cognition and decreases SUMO-2/3 conjugation

Abstract

Sepsis is characterized by multiple organ dysfunction, dysregulation of the response to the infection process, and a high mortality rate in intensive care units. In addition, individuals who overcome sepsis often manifest cognitive deficits associated with neuroinflammation resulting from the entry of pro-inflammatory cytokines into the brain. Post-translational protein modifications, such as SUMOylation, can regulate the expression of pro-inflammatory genes during sepsis. Since SUMO-2/3 can play a role in pathological conditions, our aim was to investigate a potential link between sepsis-induced cognitive decline and SUMOylation by this isoform. Firstly, the cecal slurry model was induced by intraperitoneally injecting male Swiss mice with different volumes of a cecal solution. Following assessment of body temperature, mass and septic scores, the groups that received 300 μL and 350 μL of the cecal solution were selected for the behavioural tests, as they presented signs of sepsis without excessive mortality. Surviving animals were evaluated for cognition/memory and anxious/depressive-like behaviours through the open-field, object recognition, Y-maze, and tail suspension tests. Subsequently, SUMO-2/3 conjugation was determined in samples from the hippocampus and prefrontal cortex by Western blotting. Mice in the septic groups showed decreased locomotor activity, anxious-and depressive-like behaviours, as well as impaired memory. These deficits were accompanied by a decrease in SUMO-2/3 conjugation in the hippocampus and prefrontal cortex at 24 h and 10 days after the induction of the cecal slurry model. Taken together, our findings suggest that SUMOylation is impaired in septic animals and this could be related to the behavioural deficits seen in the surviving mice.