Reciprocal MicroRNA Expression in Mesocortical Circuit and Its Interplay with Serotonin Transporter Define Resilient Rats in the Chronic Mild Stress

Prolonged stress perturbs physiological balance of a subject and thus can lead to depression. Nevertheless, some individuals are more resilient to stress than the others. Defining molecular factors underlying resilience to stress may contribute to the development of a new antidepressant strategy based on the restoration of resilient phenotype in depressed subjects. We used chronic mild stress (CMS) paradigm—well-characterized animal model of depression which caused in rats behavioral deficits (anhedonia) manifested by decreased consumption of sucrose solution. CMS also generated a proportion of resilient rats which did not alter sucrose consumption despite being stressed. Recently, regulation of a gene expression associated with microRNA (miRNA) is considered as an important factor modulating biochemical response to stress. Based on our previous work and literature survey, we investigated changes in the expression level of seven miRNAs (i.e., miR-18a-5p, miR-34a-5p, miR-135a-5p, miR-195-5p, miR-320-3p, miR-674-3p, miR-872-5p) in mesocortical circuit—crucially involved in stress response in order to find differences between susceptible and resilient phenotype. Bioinformatic analysis showed that all miRNAs of interest potentially target serotonin transporter (SERT). Chronic stress caused global increase in the expression of the abovementioned miRNAs in ventral tegmental area (VTA) of stressed rats followed by parallel decrease in miRNA expression in prefrontal cortex (PCx). This effect was more profound in resilient than anhedonic animals. Moreover, we observed decreased level of SERT in VTA of resilient rats. Our findings show that mesocortical circuit is involved in the response to stress and this phenomenon is more efficient in resilient animals.