In a captivating episode featuring Dr. Gallitano, the audience is taken on a deep dive into the intricate relationship between the Serotonin 2A receptors (5-HT2ARs) and their potential role in schizophrenia—a mental disorder marked by perceptual and cognitive anomalies. Dr. Gallitano shares pivotal findings that highlight how sleep deprivation, a commonplace environmental stimulus, can significantly amplify the levels of 5-HT2AR in the mouse frontal cortex in a mere span of hours. The linchpin in this discovery is the gene transcription factor "early growth response 3 (Egr3)," which was found to be critical for this upregulation. Further explorations reveal that EGR3 protein directly interacts with the promoter of the Htr2a gene, the gene responsible for encoding 5-HT2AR, thereby modulating its levels in the cortex. Delving into post-mortem gene expression data, it becomes evident that both EGR3 and HTR2A mRNA are diminished in schizophrenia patients, hinting at a potential linkage. This episode sheds light on a plausible mechanism by which everyday environmental factors might tweak receptor levels in the brain, influencing the manifestation and possible treatment pathways for mental disorders.

Keywords: Serotonin 2A receptors (5-HT2ARs), psychedelic drugs, schizophrenia, sleep deprivation, early growth response 3 (Egr3), frontal cortex, gene transcription, Htr2a gene, environmental stimuli, mental illness treatment.

http://dx.doi.org/10.1038/s41380-021-01390-w