Reactivation of a dormant developmental plasticity program drives synaptic rejuvenation and antidepressant-like responses

Chronic fluoxetine treatment reactivates juvenile-like plasticity in the dentate gyrus, promoting synaptic rejuvenation and reducing fear generalization in mood disorder models.

• Why it matters: Understanding how SSRIs exert their therapeutic effects is crucial, as their molecular mechanisms remain largely unknown, limiting targeted treatment development for mood and anxiety disorders.
• What they did: The study used transcriptomic analysis and enzymatic ECM degradation in Mus musculus to show that fluoxetine upregulates juvenile plasticity markers like SOX11 and BDNF, remodeling the ECM and enhancing synaptic structure.
• The result: Reactivating developmental plasticity through ECM remodeling mitigates stress-induced fear responses, highlighting a potential pathway for antidepressant efficacy and new therapeutic strategies.