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Charleston, SC — A groundbreaking study by neuroscientists at the Medical University of South Carolina (MUSC) reveals a new genetic mechanism involved in how emotional experiences shape behavior. Published in Science, the research shows that a specific type of RNA, known as long non-coding enhancer RNA (Inc-eRNA), plays a crucial role in the brain’s response to emotional stress and drug use. This discovery could open doors to new RNA-based therapies for treating psychiatric disorders.
The team, led by Dr. Christopher Cowan, professor and chair of the Department of Neuroscience, and Dr. Makoto Taniguchi, assistant professor, focused on understanding how emotional experiences—such as chronic stress or drug addiction—lead to long-lasting changes in behavior. Their findings indicate that these experiences may influence the brain through a unique genetic process involving RNA and DNA interactions.
The researchers studied the NPAS4 gene, which has been linked to both stress-induced anhedonia (the inability to experience pleasure) and drug relapse. Their experiments uncovered that the formation of an RNA:DNA “sandwich,” known as an R-loop, within the regulatory regions of NPAS4 is essential for triggering gene activation in response to emotional stimuli.
“When emotional experiences occur, specific genes need to be activated in the brain to help us adapt our behavior,” said Cowan. “R-loops bring together the enhancer region of the gene with the promoter region, allowing the gene to be switched on, thus facilitating the brain’s response to these emotional events.”
Through their preclinical mouse model, the team showed that blocking the formation of R-loops in the brain’s nucleus accumbens and prefrontal cortex prevented the animals from displaying behaviors typically seen in response to cocaine use and chronic stress. This suggests that disrupting R-loop formation could be a potential strategy for treating substance use and mood disorders, conditions often linked to maladaptive responses to emotional experiences.
In their study, the researchers found that when the R-loop mechanism was blocked, mice exhibited reduced drug-seeking behavior and increased resilience to stress. These findings are significant, as they suggest that altering the genetic regulatory processes in the brain may offer new therapeutic approaches for individuals struggling with psychiatric conditions such as depression and addiction.
The study’s co-author, Rose Marie Akiki, an M.D.-Ph.D. student at MUSC, explained, “Neural circuits in the brain need to adapt in response to experience. By understanding how this genetic mechanism works, we can begin to explore how emotional experiences shape these circuits and influence behavior.”
The research team’s discovery is particularly exciting because it shows that the regulatory RNA mechanisms involved are conserved across species, highlighting their evolutionary significance. Akiki noted that R-loops have been found in other cell types, including immune cells, where they play a role in immune responses.
The team now aims to explore the broader impact of this genetic mechanism on brain function and its potential disruption in psychiatric diseases. “We want to understand how widespread this process is in the brain and how it might be altered in different pathologies,” Taniguchi added.
This study marks an important step forward in the field of neuroscience, offering new insights into how our genes regulate behavior in response to emotional experiences. As scientists continue to unlock the mysteries of the brain’s genetic processes, this discovery could pave the way for innovative RNA-based treatments for a variety of mental health disorders.
For more information, see the full study in Science (DOI: 10.1126/science.adp1562).
