Collapsin response mediator protein 5 (CRMP5) modulates susceptibility to chronic social defeat stress in mice

Collapsin response mediator protein 5 (CRMP5), a member of the CRMP family, is expressed in the brain, particularly in the hippocampus, an area of the brain that can modulate stress responses. Social stress has a well-known detrimental effect on health and can lead to depression, but not all individuals are equally sensitive to stress. To date, researchers have not conclusively determined how social stress increases the susceptibility of the brain to depression. Here, we used the chronic social defeat stress (CSDS) model and observed higher hippocampal CRMP5 expression in stress-susceptible (SS) mice than in control and stress-resilient (RES) mice. A negative correlation was observed between the expression levels of CRMP5 and the social interaction (SI) ratio. Reduced hippocampal CRMP5 expression increased the SI ratio in SS mice, whereas CRMP5 overexpression was sufficient to induce social avoidance behaviors in control mice following exposure to subthreshold social stress induced by lentivirus-based overexpression and inducible tetracycline-on strategies to upregulate CRMP5. Interestingly, increased CRMP5 expression in SS and lenti-CRMP5-treated mice also caused serum corticosterone concentrations to increase. These findings improve our understanding of the potential mechanism by which CRMP5 triggers susceptibility to social stress, and they support the further development of therapeutic agents for the treatment of stress disorders in humans.

Automated summary

CRMP5 expression in the hippocampus was increased in stress-susceptible mice compared to control and stress-resilient mice, with a negative correlation between CRMP5 levels and social interaction ratio. Lowering hippocampal CRMP5 levels improved social interactions in stress-susceptible mice, while overexpression of CRMP5 induced social avoidance behaviors. Furthermore, increased CRMP5 expression also elevated serum corticosterone concentrations in stress-susceptible and CRMP5-treated mice. These findings shed light on how CRMP5 may contribute to susceptibility to social stress and suggest potential therapeutic targets for stress disorders in humans.