Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions | Zendy

Franck Oury | Zendy; Lori Khrimian | Zendy; Christine A. Denny | Zendy; Antoine Gardin | Zendy; Alexandre Chamouni | Zendy; Nick Goeden | Zendy; Yung-yu Huang | Zendy; Hojoon Lee | Zendy; Prashanth Nuggehalli Srinivas | Zendy; XiaoBing Gao | Zendy; Shigetomo Suyama | Zendy; Thomas Langer | Zendy; John. J. Mann | Zendy; Tamas L. Horváth | Zendy; Alexandre Bonnin | Zendy; Gérard Karsenty | Zendy

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Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions

Author(s) -

Franck Oury,

Lori Khrimian,

Christine A. Denny,

Antoine Gardin,

Alexandre Chamouni,

Nick Goeden,

Yung-yu Huang,

Hojoon Lee,

Prashanth Nuggehalli Srinivas,

XiaoBing Gao,

Shigetomo Suyama,

Thomas Langer,

John. J. Mann,

Tamas L. Horváth,

Alexandre Bonnin,

Gérard Karsenty

Publication year - 2013

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2013.08.042

Subject(s) - osteocalcin , endocrinology , biology , medicine , offspring , brainstem , placenta , osteoblast , hormone , fetus , neuroscience , pregnancy , genetics , biochemistry , alkaline phosphatase , enzyme , in vitro

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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