Using the Unpredictable Chronic Mild Stress Model in Mice to Understand the Involvement of DNA/RNA Oxidation in Major Depressive Disorder

Major Depressive Disorder (MDD) is a debilitating illness, associated with chronic development and a highly heterogeneous etiology. Despite unclear mechanisms, chronic stress is implicated in its development and/or progression. Previous studies in patients with MDD have reported chronic stress and elevated levels of oxidative stress, including increased DNA/RNA oxidation in post-mortem analyses in brain regions associated with cognitive and emotional processing. Using a preclinical model of chronic stress, this thesis investigates: 1) whether unpredictable chronic mild stress (UCMS) in mice induces neuronal DNA/RNA oxidation in the frontal cortex (FC) and basolateral amygdala (BLA), and 2) correlations between levels of neuronal DNA/RNA oxidation with depressive-like behaviors. We predicted that mice subjected to UCMS, relative to mice not subjected to the stress would present higher levels of neuronal DNA/RNA oxidation, and this would be associated with anxiety/depressive-like behaviors. This work provides a translational perspective for the involvement of DNA/RNA oxidation in MDD.M.Sc