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Gpr158 mediates osteocalcin’s regulation of cognition

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. Her...

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Autores principales: Khrimian, Lori, Obri, Arnaud, Ramos-Brossier, Mariana, Rousseaud, Audrey, Moriceau, Stéphanie, Nicot, Anne-Sophie, Mera, Paula, Kosmidis, Stylianos, Karnavas, Theodoros, Saudou, Frederic, Gao, Xiao-Bing, Oury, Franck, Kandel, Eric, Karsenty, Gerard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626410/
https://www.ncbi.nlm.nih.gov/pubmed/28851741
http://dx.doi.org/10.1084/jem.20171320
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author Khrimian, Lori
Obri, Arnaud
Ramos-Brossier, Mariana
Rousseaud, Audrey
Moriceau, Stéphanie
Nicot, Anne-Sophie
Mera, Paula
Kosmidis, Stylianos
Karnavas, Theodoros
Saudou, Frederic
Gao, Xiao-Bing
Oury, Franck
Kandel, Eric
Karsenty, Gerard
author_facet Khrimian, Lori
Obri, Arnaud
Ramos-Brossier, Mariana
Rousseaud, Audrey
Moriceau, Stéphanie
Nicot, Anne-Sophie
Mera, Paula
Kosmidis, Stylianos
Karnavas, Theodoros
Saudou, Frederic
Gao, Xiao-Bing
Oury, Franck
Kandel, Eric
Karsenty, Gerard
author_sort Khrimian, Lori
collection PubMed
description 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.
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spelling pubmed-56264102018-04-02 Gpr158 mediates osteocalcin’s regulation of cognition Khrimian, Lori Obri, Arnaud Ramos-Brossier, Mariana Rousseaud, Audrey Moriceau, Stéphanie Nicot, Anne-Sophie Mera, Paula Kosmidis, Stylianos Karnavas, Theodoros Saudou, Frederic Gao, Xiao-Bing Oury, Franck Kandel, Eric Karsenty, Gerard J Exp Med Research Articles 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. The Rockefeller University Press 2017-10-02 /pmc/articles/PMC5626410/ /pubmed/28851741 http://dx.doi.org/10.1084/jem.20171320 Text en © 2017 Khrimian et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Khrimian, Lori
Obri, Arnaud
Ramos-Brossier, Mariana
Rousseaud, Audrey
Moriceau, Stéphanie
Nicot, Anne-Sophie
Mera, Paula
Kosmidis, Stylianos
Karnavas, Theodoros
Saudou, Frederic
Gao, Xiao-Bing
Oury, Franck
Kandel, Eric
Karsenty, Gerard
Gpr158 mediates osteocalcin’s regulation of cognition
title Gpr158 mediates osteocalcin’s regulation of cognition
title_full Gpr158 mediates osteocalcin’s regulation of cognition
title_fullStr Gpr158 mediates osteocalcin’s regulation of cognition
title_full_unstemmed Gpr158 mediates osteocalcin’s regulation of cognition
title_short Gpr158 mediates osteocalcin’s regulation of cognition
title_sort gpr158 mediates osteocalcin’s regulation of cognition
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626410/
https://www.ncbi.nlm.nih.gov/pubmed/28851741
http://dx.doi.org/10.1084/jem.20171320
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