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May 28 2025
7Serotonin is widely recognized as a mood-regulating neurotransmitter, forming the basis of many antidepressant treatments. Yet, more than 90% of the body’s serotonin is produced in the gastrointestinal tract, where it functions hormonally to support digestion. This gut-based production has led scientists to suspect that serotonin might be a key mediator of gut-brain communication, potentially affecting mental health and cognitive functions.
What has remained unclear is how serotonin produced in the gut might travel to the brain, especially since the blood-brain barrier blocks many substances from entering the central nervous system. Cristina Limatola, a neuroscientist at Sapienza University of Rome, set out to explore this question. In a new study published in Cell Reports, Limatola and her team identify platelets—small, clot-forming blood components—as likely candidates for transporting serotonin to the brain.
Although platelets are primarily known for their role in blood clotting, they also absorb serotonin from the gut, store it in granules, and release it upon activation. Interestingly, Limatola’s team did not initially focus on platelets. Their research began with natural killer (NK) cells, a type of immune cell known to combat viruses and cancer. Previous findings had shown that NK cells could access the brain and influence neural circuits related to anxiety and memory by releasing interferons and neurotransmitters.
In their earlier experiments, mice lacking NK cells exhibited bolder behavior and struggled with object recognition. This led the researchers to question whether NK cells also influence serotonin-related brain activity, especially in the hippocampus—a region essential for forming fear-related memories.
In the current study, mice with depleted NK cells were more likely to freeze when exposed to a loud noise linked to an electric shock, suggesting heightened fear responses. These mice also showed lower serotonin levels in the hippocampus. Notably, the team found no changes in the brain's own serotonin-producing neurons, suggesting the serotonin deficit originated elsewhere—possibly the gut.
This prompted the researchers to investigate how serotonin might reach the brain. Their attention turned to platelets, which, while unable to cross the blood-brain barrier themselves, can release microvesicles—tiny fragments that do enter the brain. Fluorescent labeling confirmed that these platelet-derived microvesicles are present in the hippocampus. Furthermore, when NK cells were depleted, fewer platelet microvesicles were observed in this brain region.
The researchers went a step further by using an antibody to deplete platelets in mice. This led to an even stronger fear response than NK cell depletion alone. Subsequent tests revealed two key effects of NK cell depletion: reduced serotonin production in the gut and diminished expression of a protein that enables platelets to absorb serotonin. This dual reduction appeared to limit the amount of serotonin reaching the brain.
To assess the functional impact, the team measured the activity of inhibitory neurons responsible for regulating fear circuits in the hippocampus. They found that platelet depletion suppressed these neurons' activity, but administering serotonin restored it—further supporting the link between platelet-transported serotonin and fear regulation.
Limatola believes these findings offer compelling evidence that the gut, immune system, and brain are interconnected through platelet-mediated serotonin transport. Future studies will aim to trace labeled serotonin from the gut to the brain to confirm this pathway definitively.
Mac Shine, a neuroscientist from the University of Sydney, praised the work, suggesting it could pave the way for using platelets as targeted delivery systems for brain therapies.
Beyond potential clinical applications, Limatola emphasizes the broader message of the research: the body’s systems are deeply intertwined. “Our life habits can change also our brain function,” she noted, underscoring the impact of physical health on mental well-being.
Source: https://www.the-scientist.com/platelets-may-fine-tune-fear-responses-by-carrying-serotonin-to-the-brain-72985
This is non-financial/medical advice and made using AI so could be wrong.
