Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

Abstract Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger...

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Autores principales:	Maria Gerasimenko, Stanislav M. Cherepanov, Kazumi Furuhara, Olga Lopatina, Alla B. Salmina, Anna A. Shabalova, Chiharu Tsuji, Shigeru Yokoyama, Katsuhiko Ishihara, Charles Brenner, Haruhiro Higashida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2c0923f4072493b8dda2df22fce9bb6
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spelling	oai:doaj.org-article:e2c0923f4072493b8dda2df22fce9bb62021-12-02T17:45:03ZNicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder10.1038/s41598-019-57236-72045-2322https://doaj.org/article/e2c0923f4072493b8dda2df22fce9bb62020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-57236-7https://doaj.org/toc/2045-2322Abstract Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, a sister protein of CD38, has been considered a candidate mediator for the production and release of OT and its social engagement and anti-anxiety functions. However, the limited expression of CD157 in the adult mouse brain undermined confidence that CD157 is an authentic and/or actionable molecular participant in OT-dependent social behaviour. Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD). NAD is the substrate for the CD157- and CD38-dependent production of cADPR. Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR- and OT-forming deficits to overcome these deficits and function more normally.Maria GerasimenkoStanislav M. CherepanovKazumi FuruharaOlga LopatinaAlla B. SalminaAnna A. ShabalovaChiharu TsujiShigeru YokoyamaKatsuhiko IshiharaCharles BrennerHaruhiro HigashidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Gerasimenko Stanislav M. Cherepanov Kazumi Furuhara Olga Lopatina Alla B. Salmina Anna A. Shabalova Chiharu Tsuji Shigeru Yokoyama Katsuhiko Ishihara Charles Brenner Haruhiro Higashida Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
description	Abstract Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, a sister protein of CD38, has been considered a candidate mediator for the production and release of OT and its social engagement and anti-anxiety functions. However, the limited expression of CD157 in the adult mouse brain undermined confidence that CD157 is an authentic and/or actionable molecular participant in OT-dependent social behaviour. Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD). NAD is the substrate for the CD157- and CD38-dependent production of cADPR. Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR- and OT-forming deficits to overcome these deficits and function more normally.
format	article
author	Maria Gerasimenko Stanislav M. Cherepanov Kazumi Furuhara Olga Lopatina Alla B. Salmina Anna A. Shabalova Chiharu Tsuji Shigeru Yokoyama Katsuhiko Ishihara Charles Brenner Haruhiro Higashida
author_facet	Maria Gerasimenko Stanislav M. Cherepanov Kazumi Furuhara Olga Lopatina Alla B. Salmina Anna A. Shabalova Chiharu Tsuji Shigeru Yokoyama Katsuhiko Ishihara Charles Brenner Haruhiro Higashida
author_sort	Maria Gerasimenko
title	Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
title_short	Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
title_full	Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
title_fullStr	Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
title_full_unstemmed	Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
title_sort	nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of cd157 mutants in a mouse model of autism spectrum disorder
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e2c0923f4072493b8dda2df22fce9bb6
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Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder

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