Use of another mouse model indicated that bone mass accrual through brain-derived serotonin occurs by a decrease in sympathetic tone. The brain-derived serotonin apparently uses the Htr2c receptor—the most abundant serotonergic receptor in the hypothalamus—that mediates brain serotonin regulation of bone mass, a function that is independent of its influence through the same receptor on energy metabolism, the researchers reported in Cell.
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Studies using a different mouse model indicated that brain-derived serotonin acts on ventromedial hypothalamic neurons through Htr2c “to decrease sympathetic activity and to favor bone mass accrual,” Dr. Karsenty said.
Dr. Karsenty and colleagues reported that their understanding of regulation of bone mass by serotonin led to unexpected observations. First, “depending on its site of synthesis, serotonin regulates bone mass accrual in opposite directions: it inhibits it when synthesized in the duodenum and favors it when acting as a neurotransmitter.”1 They noted that this seems to be the first example of a molecule that has different influences on bone remodeling that is dependent on the site of synthesis.
The second unexpected observation was that, even though brain-derived serotonin represents only about 5% of the total pool of serotonin in the body, its influence on bone remodeling “is dominant over that exerted by gut-derived serotonin. Since [brain-derived serotonin] is regulated by leptin, these results infer that leptin regulation of bone mass is more important than the one exerted by gut-derived serotonin.”
Based on that observation, the researchers predict that “using leptin as a treatment for obesity would favor the appearance of osteoporosis.”1
Kathy Holliman is a medical journalist based in New Jersey.