Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models

Abstract Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patien...

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Autores principales:	Machi Horiai, Ayano Otsuka, Shizu Hidema, Yuichi Hiraoka, Ryotaro Hayashi, Shinji Miyazaki, Tamio Furuse, Hiroaki Mizukami, Ryoichi Teruyama, Masaru Tamura, Haruhiko Bito, Yuko Maejima, Kenju Shimomura, Katsuhiko Nishimori
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/877a9c53f90b4d71bd32daef8a710a3a
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spelling	oai:doaj.org-article:877a9c53f90b4d71bd32daef8a710a3a2021-12-02T11:57:57ZTargeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models10.1038/s41598-020-79109-02045-2322https://doaj.org/article/877a9c53f90b4d71bd32daef8a710a3a2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79109-0https://doaj.org/toc/2045-2322Abstract Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3 R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.Machi HoriaiAyano OtsukaShizu HidemaYuichi HiraokaRyotaro HayashiShinji MiyazakiTamio FuruseHiroaki MizukamiRyoichi TeruyamaMasaru TamuraHaruhiko BitoYuko MaejimaKenju ShimomuraKatsuhiko NishimoriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Machi Horiai Ayano Otsuka Shizu Hidema Yuichi Hiraoka Ryotaro Hayashi Shinji Miyazaki Tamio Furuse Hiroaki Mizukami Ryoichi Teruyama Masaru Tamura Haruhiko Bito Yuko Maejima Kenju Shimomura Katsuhiko Nishimori Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
description	Abstract Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3 R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.
format	article
author	Machi Horiai Ayano Otsuka Shizu Hidema Yuichi Hiraoka Ryotaro Hayashi Shinji Miyazaki Tamio Furuse Hiroaki Mizukami Ryoichi Teruyama Masaru Tamura Haruhiko Bito Yuko Maejima Kenju Shimomura Katsuhiko Nishimori
author_facet	Machi Horiai Ayano Otsuka Shizu Hidema Yuichi Hiraoka Ryotaro Hayashi Shinji Miyazaki Tamio Furuse Hiroaki Mizukami Ryoichi Teruyama Masaru Tamura Haruhiko Bito Yuko Maejima Kenju Shimomura Katsuhiko Nishimori
author_sort	Machi Horiai
title	Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
title_short	Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
title_full	Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
title_fullStr	Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
title_full_unstemmed	Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
title_sort	targeting oxytocin receptor (oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/877a9c53f90b4d71bd32daef8a710a3a
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Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models

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