The research, published in the journal Advanced Science, identifies a new strategy to target the biological origin of post-traumatic stress disorder (PTSD). PTSD can develop after a traumatic experience and is characterized by intrusive memories, often accompanied by intense fear. Currently, treatments focus on alleviating symptoms rather than directly addressing their origin.
The study focuses on the brain protein CPEB3, which acts as a molecular switch essential for memory consolidation. After learning, CPEB3 changes state and forms stable amyloid structures that maintain long-term memories. Although the term amyloid is associated with neurodegenerative diseases, those formed by CPEB3 play a normal role in memory preservation.
Using a small synthetic protein, QBP1, researchers observed that it hinders the amyloid aggregation of CPEB3. In genetically modified mice producing QBP1, long-term memory consolidation was altered. While initial learning and short-term memory remained intact, the ability to recall long-term was affected, both in object recognition and spatial memory tests.
In fear-associated tests, animals producing QBP1 showed a reduced persistence of fear responses and a decrease in anhedonia (difficulty experiencing pleasure), characteristic symptoms of PTSD. Hippocampal analysis revealed a lower presence of the CPEB3 molecular switch. Advanced proteomic studies confirmed QBP1's high specificity and safety, with no unwanted interactions or side effects.
The work, led by researcher Mariano Carrión-Vázquez, serves as a proof of concept in mice. The early preclinical phase will explore intranasal administration of QBP1 in normal mice to test its acute application after a traumatic experience. This finding opens avenues for preventing and treating PTSD by targeting memory consolidation mechanisms and suggests future applications combined with psychological therapies.
