Abstract:
Researchers have identified a genetic mechanism that regulates behavioral adaptations to emotional experiences through the formation of R-loops, RNA:DNA structures that activate specific genes. The study, focused on the NPAS4 gene — associated with stress and drug addiction — revealed that blocking R-loops prevents maladaptive behaviors, such as cocaine-seeking and stress-induced anhedonia, in mice.
These findings suggest that emotional experiences alter brain circuits by modulating gene expression via regulatory RNA. Implications include the potential for RNA-based therapies in the treatment of psychiatric disorders linked to stress and substance use.
Main points of the research:
- Function of R-loops: These RNA:DNA structures activate genes such as NPAS4 in response to emotional experiences.
- Behavioral impact: Blocking R-loops in brain regions prevented drug- and stress-related behaviors in mice.
- Therapeutic potential: Insights could lead to the development of RNA-based treatments for mood disorders and addiction.
Study details
Researchers at the Medical University of South Carolina (MUSC) have identified a genetic regulatory mechanism in preclinical models that links emotional experiences to behavioral changes. The study, published in the journal Science, investigated the role of R-loops in activating the NPAS4 gene.
R-loops help activate specific genes by forming an RNA:DNA structure that brings the enhancer region and promoter of the gene closer together to facilitate their activation. When researchers blocked the formation of these R-loops in the nucleus accumbens of mice, the animals did not develop drug-seeking behaviors. In a similar manipulation in the prefrontal cortex, the mice did not exhibit stress-induced anhedonia.
“These findings reveal how emotional experiences can trigger changes in the brain, linking genetic alterations to adaptive or maladaptive behaviors,” said Dr. Christopher Cowan, chair of MUSC’s Department of Neuroscience.
Furthermore, the study highlighted that the R-loops formed by regulatory RNA are highly conserved across species, indicating their evolutionary relevance.
Therapeutic potential
The research suggests that the R-loop mechanism could be harnessed to develop new RNA-based therapies, targeting psychiatric disorders and addiction. “Understanding how these fundamental genetic processes operate is essential to creating more effective and personalized treatments,” Cowan said.
Next steps
The researchers are now seeking to understand the extent of this mechanism in the brain and its stability in pathological conditions. “If this mechanism is truly ubiquitous, it could open doors to new therapeutic approaches in a variety of psychiatric conditions,” explained Dr. Makoto Taniguchi, assistant professor in the MUSC Department of Neuroscience.
This discovery expands our understanding of how the brain interprets emotionally meaningful experiences to shape adaptive behaviors and offers a new avenue for RNA-based therapies.
Reference:
Taniguchi, M., Akiki, R. M., & Cowan, C. (2024). Enhancer RNA-driven R-loops modulate NPAS4 gene expression to control stress-induced behaviors. Science.
Dr. Fabiano de Abreu Agrela Rodrigues MRSB holds a post-PhD in Neuroscience and is an elected member of Sigma Xi – The Scientific Research Honor Society (more than 200 members of Sigma Xi have received the Nobel Prize), as well as being a member of the Society for Neuroscience in the United States, the Royal Society of Biology and The Royal Society of Medicine in the United Kingdom, the European Society of Human Genetics in Vienna, Austria, and the APA – American Philosophical Association in the United States. He holds a Master’s degree in Psychology and a Bachelor’s degree in History and Biology. He is also a Technologist in Anthropology and Philosophy, with several national and international degrees in Neuroscience and Neuropsychology. Dr. Fabiano is a member of prestigious high IQ societies, including Mensa International, Intertel, ISPE High IQ Society, Triple Nine Society, ISI-Society, and HELLIQ Society High IQ. He is the author of more than 300 scientific studies and 30 books. He is currently a visiting professor at PUCRS in Brazil, UNIFRANZ in Bolivia and Santander in Mexico. He also serves as Director of CPAH – Centro de Pesquisa e Análises Heráclito and is the creator of the GIP project, which estimates IQ through the analysis of genetic intelligence. Dr. Fabiano is also a registered journalist, having his name included in the book of records for achieving four records, one of which is for being the greatest creator of characters in the history of the press.