Using a mouse model, the researchers found that PTH from the peripheral system is associated with the SFO, a circular ventricular organ that lacks a blood-brain barrier. Brain slice electrophysiology and calcium fluorescence studies showed that peripheral PTH activated SFO neurons.

Researchers have identified Expression of PTH receptors in SFO neurons. Knockdown of PTH receptor 1 reduced basal PTH levels in mice and their response to peripheral calcium stimulation.


“These results suggest that the central nervous system (CNS) senses circulating PTH, and PTH sensing from the brain is also necessary when regulating serum PTH,” said Professor YANG Fan from SIAT, corresponding author of the study.

In addition, the researchers studied Can stimulation of SFO neurons modulate peripheral PTH levels? Both GABAergic and glutamatergic neurons were activated by chemogenetic technology.

Stimulation of inhibitory GABAergic neurons caused a decrease in serum PTH and decreased trabecular bone density, whereas stimulation of excitatory glutamatergic neurons had the opposite effect.

Investigating the neuroendocrine link in brain-bone metabolism

“We note that GABAergic neurons predominate in SFO cells expressing PTH receptor 1, and glutamatergic neurons in cells expressing PTH receptor 2,” said Prof.

The research team also examined the brain nucleus downstream of the SFO. They found that paraventricular nucleus (PVN) Also the hypothalamus, which receives a GABAergic projection from the SFO modulates serum PTH levels and trabecular bone metabolism.

Previous studies have generally focused on afferent and efferent nerve fibers surrounding bones when discussing brain-bone connections. Current researchers have discovered that chemical signaling through the endocrine system also plays an important role in brain-bone communication.

“Traditionally, the subfornical organ is considered to be the center of water-salt balance. Our study shows that the SFO is much more than that. The loose structure of the blood-brain barrier in the SFO gives it various abilities to sense peripheral humoral hormones. “The first author of the study, Dr. ZHANG Lu said. “We expect that other ventricular organs should also be more active in the process of interoception.”

This research reveals critical role of the brain-parathyroid-bone axis in maintaining homeostasis of bone metabolism. It also provides new insights into how bone homeostasis is maintained.

Source: Eurekalert

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