SAHA Improves Depressive Symptoms, Cognitive Impairment and Oxidative Stress: Rise of a New Antidepressant Class

Depression is a disabling psychiatric disorder affecting millions of people all around the world. Under current therapeutic choices, a portion of patients are not responsive, have relapses, or experience cognitive side effects. Hence, the present study aimed to find other antidepressant compounds lacking the mentioned deficiency. Since epigenetic regulations have attracted more attention in etiology of depression, histone deacetylase (HDAC) inhibitors have gained more importance due to their possible antidepressant activity. We selected a promising member of HDAC inhibitors named suberanilohydroxamic acid (SAHA) to evaluate its antidepressant properties. Early life stress disarrays many neurodevelopmental factors and consequently, leads to the destruction of hippocampus and prefrontal cortex synapses as areas highly related to emotion and memory so that any destruction on them can cause lasting impairments. For that reason, we used maternal separation (MS) paradigm to investigate depression in male mice. To compare the efficacy of SAHA with current treatment options, we also treated a group of MS mice with fluoxetine (FLX) as first-line pharmacological drugs of depression. The results demonstrated that depressive-like behavior, cognitive function and inflammatory response of MS mice were attenuated with SAHA. Our data showed that, besides anti-depressant and cognition-boosting effects similar to FLX, SAHA counteracted inflammatory response caused by depression and reversed the coenzyme Q₁₀ (CoQ₁₀) level in hippocampus. SAHA's effect on alleviating depressive behavior was accompanied with memory enhancement and hippocampus biochemical tests. These findings may propose SAHA as another therapeutic option for depressive symptoms, especially with comorbid cognitive impairment.