Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions

被引：358

作者：

Oury, Franck ^{[1
]}

Khrimian, Lori ^{[1
]}

Denny, Christine A. ^{[2
]}

Gardin, Antoine ^{[1
]}

Chamouni, Alexandre ^{[1
]}

Goeden, Nick ^{[3
]}

Huang, Yung-yu ^{[4
,5
]}

Lee, Hojoon ^{[6
]}

Srinivas, Prashanth ^{[1
]}

Gao, Xiao-Bing ^{[7
]}

Suyama, Shigetomo ^{[7
]}

Langer, Thomas ^{[8
]}

Mann, John. J. ^{[4
,5
]}

Horvath, Tamas L. ^{[7
]}

Bonnin, Alexandre ^{[3
]}

Karsenty, Gerard ^{[1
]}

机构：

[1] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[2] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[3] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA

[4] Columbia Univ, Dept Psychiat, Div Mol Imaging & Neuropathol, New York, NY 10471 USA

[5] New York State Psychiat Inst & Hosp, New York, NY 10471 USA

[6] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[7] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA

[8] Sanofi Aventis Deutschland GmbH, R&D Biotherapeut BioInnovat, D-65926 Frankfurt, Germany

来源：

CELL | 2013年 / 155卷 / 01期

关键词：

INHIBITS BONE-FORMATION; DEFICIENT MICE; CLEIDOCRANIAL DYSPLASIA; ENERGY-METABOLISM; SEROTONIN; MASS; HYDROXYLASE; EXPRESSION; INSULIN; ANXIETY;

D O I：

10.1016/j.cell.2013.08.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：228 / 241

页数：14

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