Maternal and offspring pools of osteocalcin influence brain development and functions.
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.
Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
Franck
F
Oury
Lori
L
Khrimian
Christine A
CA
Denny
Antoine
A
Gardin
Alexandre
A
Chamouni
Nick
N
Goeden
Yung-yu
YY
Huang
Hojoon
H
Lee
Prashanth
P
Srinivas
Xiao-Bing
XB
Gao
Shigetomo
S
Suyama
Thomas
T
Langer
John J
JJ
Mann
Tamas L
TL
Horvath
Alexandre
A
Bonnin
Gerard
G
Karsenty
D000375:Aging; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction
D018377:Neurotransmitter Agents; D015675:Osteocalcin