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Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions
Open accessAbstract
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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“Osteocalcin also stimulates the synthesis of monoamine neurotransmitters in the hippocampus and inhibits gamma-aminobutyric acid (GABA) synthesis, improving learning and memory skills [207].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [207]
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Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.44 · Cited by 2,023
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Metadata
- Authors
- Oury, F., Khrimian, L., Denny, C. A., Gardin, A., Chamouni, A., Goeden, N., Huang, Y.-Y., Lee, H., Srinivas, P., Gao, X.-B., Suyama, S., Langer, T., Mann, J. J., Horvath, T. L., Bonnin, A., & Karsenty, G.
- Affiliations
- Columbia University (US)
- University of Southern California (US)
- New York State Psychiatric Institute (US)
- Yale University (US)
- Sanofi (Germany) (DE)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 155
- Issue
- 1
- Pages
- 228-241
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3864001
- OpenAlex
- W2017975043
- Cited by
- 484
- References
- 58
- Citations by year
- 2026: 33 · 2025: 43 · 2024: 40 · 2023: 39 · 2022: 40 · 2021: 45 · 2020: 77 · 2019: 35 · 2018: 31 · 2017: 25 · 2016: 27 · 2015: 17 · 2014: 28 · 2013: 4
- FWCI
- 11.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Sanofi
- National Institutes of Health
- National Institute on Aging (P01AG032959)
- National Institute of General Medical Sciences (T32GM007088)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP1DK098058)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045548)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteocalcin, blood-brain barrier, GABA synthesis, anxiety, depression, learning and memory, neuronal apoptosis, placental transfer, maternal genotype, fetal brain development
- MeSH terms
- Aging, Animals, Brain, Female, Fetus, Pregnancy, Signal Transduction, Osteocalcin, Neurotransmitter Agents, Mice
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