Depression is one of the most common mental disorders worldwide, but its molecular causes remain unclear. Domestic researchers have revealed that depression can occur not only due to simple neuronal damage but also from disturbances in specific neural signaling pathways.
Professor Huh Won-do of the Korea Advanced Institute of Science and Technology (KAIST) and his research team analyzed brain tissue from patients who chose extreme measures, in collaboration with forensic physician Lee Min-joo from the National Forensic Service (NFS) and Professor Kim Seok-hwi of the pathology department at Ajou University Medical Center, and noted on the 19th that they have elucidated a new molecular mechanism of depression and proposed a way to restore antidepressant effects.
The research team also focused on a part known as the "dentate gyrus" in the hippocampus, the area of the brain responsible for memory and emotions. The dentate gyrus plays a crucial role in forming new memories when information first enters the hippocampus. It is associated with emotional regulation and depression.
In observing two mouse models with depression in a stress environment, the team found a significant increase in a signaling receptor called "FGFR1" that transmits growth and differentiation commands within cells in the dentate gyrus. In fact, mice with the FGFR1 gene removed were more vulnerable to stress and exhibited symptoms of depression more quickly. This suggests that FGFR1 plays an important role in neural regulation and stress resistance.
Subsequently, the researchers developed a system to activate FGFR1 with light. They successfully applied this system to restore antidepressant effects in a mouse model with low FGFR1 levels.
However, no effects were observed in aged mouse models of depression. In exploring the cause of this, the research team revealed that a protein known as "Numb" is excessively expressed in the aging brain, disrupting FGFR1 signaling.
Professor Huh Won-do said, "This research has significant implications by revealing that depression can arise not only from simple neuronal damage but also from disturbances in specific neural signaling pathways. Especially, it molecularly clarifies why antidepressants do not work well for elderly patients and provides clues for the future development of new treatments targeting the Numb protein."
The results of this study were published in the international journal "Experimental & Molecular Medicine" on the 15th.
References
Experimental & Molecular Medicine (2025), DOI: https://doi.org/10.1038/s12276-025-01519-9