Maternal and offspring pools of osteocalcin influence brain development and functions.

Abstract

The powerful regulation of bone mass exerted by the brain suggests the existence of bone-derived signals modulating this regulation or other functions of the brain. We show here that the osteoblast-derived hormone osteocalcin crosses the blood-brain barrier, binds to neurons of the brainstem, midbrain, and hippocampus, enhances the synthesis of monoamine neurotransmitters, inhibits GABA synthesis, prevents anxiety and depression, and favors learning and memory independently of its metabolic functions. In addition to these postnatal functions, maternal osteocalcin crosses the placenta during pregnancy and prevents neuronal apoptosis before embryos synthesize this hormone. As a result, the severity of the neuroanatomical defects and learning and memory deficits of Osteocalcin(-/-) mice is determined by the maternal genotype, and delivering osteocalcin to pregnant Osteocalcin(-/-) mothers rescues these abnormalities in their Osteocalcin(-/-) progeny. This study reveals that the skeleton via osteocalcin influences cognition and contributes to the maternal influence on fetal brain development.

• Authors: Franck Oury, Lori Khrimian, Christine A Denny, Antoine Gardin, Alexandre Chamouni, Nick Goeden, Yung-yu Huang, Hojoon Lee, Prashanth Srinivas, Xiao-Bing Gao, Shigetomo Suyama, Thomas Langer, John J Mann, Tamas L Horvath, Alexandre Bonnin, Gerard Karsenty
• Journal: Cell (Cell) Vol. 155 Issue 1 Pg. 228-41 (Sep 26 2013) ISSN: 1097-4172 [Electronic] United States
• PMID: 24074871 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Neurotransmitter Agents
• Osteocalcin

Topics

• Aging
• Animals
• Brain (embryology, growth & development, physiology)
• Female
• Fetus (metabolism)
• Mice
• Neurotransmitter Agents (metabolism)
• Osteocalcin (metabolism)
• Pregnancy
• Signal Transduction