Predictable Chronic Mild Stress Improves Mood, Hippocampal Neurogenesis and Memory

Maintenance of neurogenesis in the adult hippocampus is important for functions such as mood and memory. As exposure to unpredictable chronic stress (UCS) results in decreased hippocampal neurogenesis, enhanced depressive- and anxiety-like behaviors and memory dysfunction, it is believed that declined hippocampal neurogenesis mainly underlies the behavioral and cognitive abnormalities after UCS. However, the effects of predictable chronic mild stress (PCMS) such as the routine stress experienced in day-to-day life on functions such as mood, memory, hippocampal neurogenesis are unknown. Using forced swim and elevated plus maze tests in a prototype of adult rats, we demonstrate that PCMS (comprising 5 minutes of daily restraint stress for 28 days) decreases depressive- and anxiety-like behaviors for prolonged periods. Moreover, we illustrate that decreased depression and anxiety scores after PCMS are associated with ~1.8 fold increase in the production and growth of new neurons in the hippocampus. Additionally, we found that PCMS leads to enhanced memory function in water maze as well as novel object recognition tests. Collectively, these findings reveal that PCMS is beneficial to the adult brain function, which is exemplified by an increased hippocampal neurogenesis and an improved mood and cognitive function.