Stress is a well-known trigger of major depression and has been more recently implicated in the pathogenesis of cognitive disorders, including Alzheimer's disease.53 These pathological conditions are believed to reflect exposure of the brain to high levels of circulating glucocorticoids.2 Since we previously reported that CDK5 regulates GR transcriptional activity by phosphorylating this receptor,24 we examined in the current study the potential role of CDK5 in stress response by focusing on mouse PFC and HIPPO. Here, CDK5 is linked to major depressive disorder.