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Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Morais, Livia H. and Golubeva, Anna V. and Casey, Sophie and Scott, Karen A. and Ramos Costa, Ana Paula and Moloney, Gerard M. and Dinan, Timothy G. and Cryan, John F. (2021) Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse. Neuropsychopharmacology . ISSN 0893-133X. doi:10.1038/s41386-021-01040-3. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20210603-131135007

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Abstract

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41386-021-01040-3DOIArticle
https://rdcu.be/clS8gPublisherFree ReadCube access
ORCID:
AuthorORCID
Scott, Karen A.0000-0002-4133-423X
Moloney, Gerard M.0000-0002-3672-1390
Dinan, Timothy G.0000-0002-2316-7220
Cryan, John F.0000-0001-5887-2723
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 07 January 2021; Revised 21 April 2021; Accepted 03 May 2021; Published 26 May 2021. The authors would like to thank Dr Caitlin Cowan for assisting with paper proof reading and Dr Angela Moya-Perez, Patrick Fitzgerald, Colette Manley and the Staff of the Bioservices Unit, University College Cork for technical support. Dr Gil Sharon and Dr Jose Franco for assisting on the data analyses. This publication has emanated from research supported in part by a Centre grant from Science Foundation Ireland (SFI) to the APC Microbiome Institute under Grant Number SFI/12/RC/2273_P2. It was funded from the European Community’s Seventh Framework Programme Grant MyNewGut under Grant Agreement No. FP7/2007–2013 and Dept Agriculture, Food & the Marine, Ireland funded TODDLERFOOD: Food Solutions for Replenishing Disrupted Microbiota in Toddlers (2014–2018) and SMARTFOOD: Science Based ‘Intelligent’/Functional and Medical Foods for Optimum Brain Health, Targeting Depression and Cognition (2013–2017). LHM was funded by Science Without Borders, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), under the Grant Agreement Number No. 11601-13-2. The authors have nothing to disclose. Open Access funding provided by the IReL Consortium. Author Contributions: LHM and JFC conceived the idea. LHM design and performed the experiments. AG, SC, KS, APRC and GM assisted with experiments. LHM wrote the paper. All the authors contributed to the final version of the paper. AG and GM helped supervise the project. TD and JFC supervised the project.
Funders:
Funding AgencyGrant Number
Science Foundation, IrelandSFI/12/RC/2273_P2
European Research Council (ERC)FP7/2007-2013
Department of Agriculture, Food and the Marine (Ireland)UNSPECIFIED
Science Without BordersUNSPECIFIED
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)11601-13-2
IReL ConsortiumUNSPECIFIED
DOI:10.1038/s41386-021-01040-3
Record Number:CaltechAUTHORS:20210603-131135007
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210603-131135007
Official Citation:Morais, L.H., Golubeva, A.V., Casey, S. et al. Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-01040-3
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109372
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Jun 2021 21:09
Last Modified:03 Jun 2021 21:09

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