Bidirectional control of parathyroid hormone and bone mass by subfornical organ

Lu Zhang; Nian Liu; Jie Shao; Dashuang Gao; Yunhui Liu; Yingzi Zhao; Chuanliang Han; Di Chen; Liping Wang; William Weijia Lu; Fan Yang

doi:10.1016/j.neuron.2023.03.030

Bidirectional control of parathyroid hormone and bone mass by subfornical organ

Neuron. 2023 Jun 21;111(12):1914-1932.e6. doi: 10.1016/j.neuron.2023.03.030. Epub 2023 Apr 20.

Authors

Lu Zhang¹, Nian Liu², Jie Shao³, Dashuang Gao³, Yunhui Liu³, Yingzi Zhao³, Chuanliang Han³, Di Chen⁴, Liping Wang⁵, William Weijia Lu⁶, Fan Yang⁷

Affiliations

¹ The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, China.
² The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
³ The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁴ Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁵ The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, Shenzhen, Guangdong, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, China.
⁶ Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, China; Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: wwlu@hku.hk.
⁷ The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, Shenzhen, Guangdong, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, China. Electronic address: fan.yang@siat.ac.cn.

PMID: 37084721
DOI: 10.1016/j.neuron.2023.03.030

Abstract

Parathyroid hormone (PTH) is one of the most important hormones for bone turnover and calcium homeostasis. It is unclear how the central nervous system regulates PTH. The subfornical organ (SFO) lies above the third ventricle and modulates body fluid homeostasis. Through retrograde tracing, electrophysiology, and in vivo calcium imaging, we identified the SFO as an important brain nucleus that responds to serum PTH changes in mice. Chemogenetic stimulation of GABAergic neurons in SFO induces decreased serum PTH followed by a decrease in trabecular bone mass. Conversely, stimulation of glutamatergic neurons in the SFO promoted serum PTH and bone mass. Moreover, we found that the blockage of different PTH receptors in the SFO affects peripheral PTH levels and the PTH's response to calcium stimulation. Furthermore, we identified a GABAergic projection from the SFO to the paraventricular nucleus, which modulates PTH and bone mass. These findings advance our understanding of the central neural regulation of PTH at cellular and circuit level.

Keywords: bone; parathyroid; subfornical organ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Fluids*
Calcium
GABAergic Neurons
Mice
Parathyroid Hormone / pharmacology
Subfornical Organ*

Substances

Parathyroid Hormone
Calcium