Format

Send to

Choose Destination
J Exp Med. 2017 Oct 2;214(10):2859-2873. doi: 10.1084/jem.20171320. Epub 2017 Aug 29.

Gpr158 mediates osteocalcin's regulation of cognition.

Author information

1
Department of Genetics and Development, Columbia University Medical Center, New York, NY.
2
Institut Necker-Enfants Malades, CS 61431, Paris, France.
3
Institut National de la Santé et de la Recherche Médicale, U1151, Paris, France.
4
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
5
Grenoble Institute des Neurosciences, Université Grenoble Alpes, Grenoble, France.
6
INSERM, U1216, Grenoble, France.
7
Department of Neuroscience, Columbia University Medical Center, New York, NY.
8
Howard Hughes Medical Institute, Columbia University, New York, NY.
9
New York State Psychiatric Institute, New York, NY.
10
CHU Grenoble Alpes, Grenoble, France.
11
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT.
12
Kavli Institute for Brain Science, Columbia University Medical Center, New York, NY.
13
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY.
14
Department of Genetics and Development, Columbia University Medical Center, New York, NY gk2172@cumc.columbia.edu.

Abstract

That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify Gpr158, an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes.

PMID:
28851741
PMCID:
PMC5626410
DOI:
10.1084/jem.20171320
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center