XMaternal and offspring pools of osteocalcin influence brain development and functions

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

doi:10.1016/j.cell.2013.08.042

XMaternal and offspring pools of osteocalcin influence brain development and functions

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^*

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

317 Scopus citations

Abstract

Summary 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.

Original language	English (US)
Pages (from-to)	228
Number of pages	1
Journal	Cell
Volume	155
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2013.08.042
State	Published - Sep 26 2013

Funding

We thank Drs. P. Ducy, C. Zuker, and R. Hen for critical reading of the manuscript or experimental advice and Drs. R. Allikmets and J. Kong for performing the electroretinogram. This work was supported by grants from the NIH (G.K.), Sanofi Aventis (G.K.), Pioneer award (T.L.H.), and Human frontier scientific program (F.O.).

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "XMaternal and offspring pools of osteocalcin influence brain development and functions",

abstract = "Summary 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.",

author = "Franck Oury and Lori Khrimian and Denny, {Christine A.} and Antoine Gardin and Alexandre Chamouni and Nick Goeden and Huang, {Yung Yu} and Hojoon Lee and Prashanth Srinivas and Gao, {Xiao Bing} and Shigetomo Suyama and Thomas Langer and Mann, {John J.} and Horvath, {Tamas L.} and Alexandre Bonnin and Gerard Karsenty",

note = "Funding Information: We thank Drs. P. Ducy, C. Zuker, and R. Hen for critical reading of the manuscript or experimental advice and Drs. R. Allikmets and J. Kong for performing the electroretinogram. This work was supported by grants from the NIH (G.K.), Sanofi Aventis (G.K.), Pioneer award (T.L.H.), and Human frontier scientific program (F.O.). ",

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AU - Oury, Franck

AU - Khrimian, Lori

AU - Denny, Christine A.

AU - Gardin, Antoine

AU - Chamouni, Alexandre

AU - Goeden, Nick

AU - Huang, Yung Yu

AU - Lee, Hojoon

AU - Srinivas, Prashanth

AU - Gao, Xiao Bing

AU - Suyama, Shigetomo

AU - Langer, Thomas

AU - Mann, John J.

AU - Horvath, Tamas L.

AU - Bonnin, Alexandre

AU - Karsenty, Gerard

N1 - Funding Information: We thank Drs. P. Ducy, C. Zuker, and R. Hen for critical reading of the manuscript or experimental advice and Drs. R. Allikmets and J. Kong for performing the electroretinogram. This work was supported by grants from the NIH (G.K.), Sanofi Aventis (G.K.), Pioneer award (T.L.H.), and Human frontier scientific program (F.O.).

PY - 2013/9/26

Y1 - 2013/9/26

N2 - Summary 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.

AB - Summary 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.

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XMaternal and offspring pools of osteocalcin influence brain development and functions

Abstract

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