Sodium Butyrate Functions as an Antidepressant and Improves Cognition with Enhanced Neurotrophic Expression in Models of Maternal Deprivation and Chronic Mild Stress

It is known that cognitive processes, such as learning and memory, are affected in depression. Several authors have described histone deacetylase (HDAC) inhibitors as a class of drugs that improve long-term memory formation. The current study examined the effects of maternal deprivation (MD) and chronic mild stress (CMS), which have been shown as animal models of depression, and the effects of sodium butyrate (SB), a HDAC inhibitor, on recognition memory. Considering that neurotrophic factors have been pointed as a key event involved in cognition and depressive disorder, levels of neurotrophic factors (BDNF, NGF and GDNF) were investigated. MD and CMS induced depressive-like behavior in the forced swimming test (FST) and memory impairment in the object recognition (OR) test, without altering locomotor activity of rats. In addition, SB was able to reverse the stress-induced neurotrophic factors decrease and reversed memory impairment. The results indicate that stress both at early and later stage of life may induce cognitive impairment in animals and neurotrophic factors (BDNF, NGF and GDNF) levels decrease. SB treatment improved the recognition memory and reversed the neurotrophins levels decreased in the hippocampus of rats submitted to the MD and CMS models. Together, our results reinforce the notion that SB displays a specific antidepressant profile and improves cognition in MD and CMS rats that may be, at least in part, due to its upregulation of neurotrophic factors.