Effects of sodium butyrate on aversive memory in rats submitted to sepsis

Epigenetic mechanisms are involved in normal behavior and are implicated in several brain neurodegenerative conditions, psychiatric and inflammatory diseases as well. Moreover, it has been demonstrated that sepsis lead to an imbalance in acetylation of histones and that histone deacetylase inhibitors (HDACi) can reverse this condition. In the present study, we evaluated the effects of a microinjection of sodium butyrate (SB, HDACi) into cerebral ventricle on aversive memory in rats submitted to the sepsis. Rats were given a single intraventricular injection of artificial cerebrospinal fluid (ACSF) or SB and immediately after the stereotaxic surgery and the drug infusion, the animals were subjected to cecal ligation and perforation (CLP). The animals were killed twenty four hours or ten days after sepsis induction and the prefrontal cortex, hippocampus, striatum and cortex were obtained to the determination of histone deacetylase activity. In a separate cohort of animals 10 days after sepsis induction, it was performed the inhibitory avoidance task. SB administration was able to reverse the impairment in aversive memory and inhibited the HDAC activity in prefrontal cortex and hippocampus 10 days after CLP. These support a role for an epigenetic mechanism in the long-term cognitive impairments observed in sepsis survivors animals.