For several decades, the prevalence of anxiety and depression has been on a steady incline globally, a situation significantly worsened by the COVID-19 pandemic. Groundbreaking research spearheaded by Frank Schroeder from the Boyce Thompson Institute is paving the way towards developing novel treatments aimed at mitigating this widespread mental health crisis.
Serotonin, a neurotransmitter identified in the 1930s and prevalent across various animal species, plays a critical role in regulating numerous behaviours, including eating, sleeping, mood, and cognitive functions. Currently, medications that modulate serotonin levels are the primary treatment for psychological conditions such as anxiety and depression, as well as eating disorders.
The nematode Caenorhabditis elegans, a tiny roundworm, is a simplified yet powerful model for neurobiological research, particularly in studying how serotonin influences behaviour and dietary habits. Traditionally, it was believed that C. elegans synthesised serotonin through a singular molecular pathway before its rapid degradation. However, Schroeder’s research team, collaborating with colleagues at Columbia University, has uncovered that these beliefs were only partially accurate.
Schroeder discovered an alternative biosynthetic pathway responsible for approximately half of the total serotonin generated in their model organism. This finding was detailed in a publication in Nature Chemical Biology on October 10.
The research, initiated about three years ago, led to the unexpected identification of an enzyme that transforms serotonin into derivative compounds. Contrary to the prevailing assumption that serotonin is swiftly broken down post-synthesis, Schroeder’s team found it serves as a precursor for other compounds, which play a part in serotonin’s known effects. This revelation prompted a deeper investigation into serotonin’s biosynthesis and its conversion into these novel molecules.
Jingfang Yu, a doctoral candidate in Schroeder’s lab and the paper’s lead author, demonstrated that these new serotonin derivatives influence feeding behaviour in worms. Without endogenous serotonin, the worms exhibit rapid movement across bacterial food sources and seldom pause to explore their environment. This behaviour, however, is mitigated when the worms are treated with serotonin derivatives, suggesting these compounds are critical contributors to effects previously attributed to serotonin itself.
C. elegans is an exemplary model for serotonin research, given the significant conservation of its molecular signalling pathways across species, including humans. Much like in humans, a considerable portion of serotonin in C. elegans is produced in the gut.
Schroeder hinted that human serotonin might undergo similar conversions into metabolites like those found in C. elegans. He posited that this breakthrough lays the groundwork for further investigation into the implications of these findings for humans.
Schroeder, who also teaches in the Department of Chemistry and Chemical Biology at Cornell University, underscored the potential for future research to explore the significance of these metabolites in humans, the comparative roles of different biosynthetic pathways, and how these pathways and metabolites influence human behaviours, particularly those related to mental health and eating.
The team is actively investigating how these newly discovered serotonin derivatives impact behaviour in C. elegans and whether analogous metabolites are present in humans, hoping to shed more light on the complex mechanisms underlying mental health and dietary behaviours.
More information: Jingfang Yu et al, Parallel pathways for serotonin biosynthesis and metabolism in C. elegans, Nature Chemical Biology. DOI: 10.1038/s41589-022-01148-7
Journal information: Nature Chemical Biology Provided by Boyce Thompson Institute
