Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects

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This preprint studied the long-term effects of developmental timing of oxytocin (OT) neuron activity by chemogenetically inhibiting OT-expressing neurons during three postnatal critical periods—infancy, juvenile stage, and young adulthood—in male and female mice, followed by longitudinal assessment of behavior and metabolic outcomes. The most pronounced behavioral effects were seen after inhibition during infancy in both sexes, with social memory impairment in males regardless of when inactivation occurred. Metabolically, adult males showed increased body weight after inhibition across cohorts, and fat mass and adipocyte size increased specifically when OT neurons were inhibited during the juvenile period; neonates also showed a delayed day of birth and altered feeding behavior after inhibition around birth. The authors note this work is a preprint and not peer reviewed. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Oxytocin (OT) is a neuromodulator of social behaviour in mammals and accumulative data support the concept of a critical period for OT action during infancy. However, it is possible that the specific functions of OT depend on different time periods of action. In this study, we aimed to determine whether there are developmental stages during which OT-expressing neurons play a decisive role with long-term consequences. To this end, we chemogenetically inhibited OT-expressing neurons during three critical periods of development (in infants, juveniles, and young adults) in male and female mice, followed by a longitudinal study to assess behaviour and metabolic perturbations. The most pronounced behavioural effects are observed after inhibition during infancy in both sexes. Notably, social memory is consistently impaired in males, regardless of the inactivation period. From a metabolic perspective, in adulthood, an increase in body weight is observed in all cohorts of males but fat mass and adipocyte size increase after inhibition of OT-expressing neurons during juvenile period. In addition, we observed a significant delay in the day of birth and an alteration in feeding behaviour in neonates after inhibiting OT-expressing neurons around the time of birth. Thus, inhibition of OT neurons during three postnatal periods has direct, distinct, and long-lasting consequences on social behaviour and metabolism, depending on the sex and on the timing of inactivation. Our results also demonstrate a role of foetal/neonate oxytocin neurons in the timing of birth and in early feeding behaviour.
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Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects Françoise Muscatelli, Fabienne Schaller, Marie-Sophie Alifrangis, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8223143/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Oxytocin (OT) is a neuromodulator of social behaviour in mammals and accumulative data support the concept of a critical period for OT action during infancy. However, it is possible that the specific functions of OT depend on different time periods of action. In this study, we aimed to determine whether there are developmental stages during which OT-expressing neurons play a decisive role with long-term consequences. To this end, we chemogenetically inhibited OT-expressing neurons during three critical periods of development (in infants, juveniles, and young adults) in male and female mice, followed by a longitudinal study to assess behaviour and metabolic perturbations. The most pronounced behavioural effects are observed after inhibition during infancy in both sexes. Notably, social memory is consistently impaired in males, regardless of the inactivation period. From a metabolic perspective, in adulthood, an increase in body weight is observed in all cohorts of males but fat mass and adipocyte size increase after inhibition of OT-expressing neurons during juvenile period. In addition, we observed a significant delay in the day of birth and an alteration in feeding behaviour in neonates after inhibiting OT-expressing neurons around the time of birth. Thus, inhibition of OT neurons during three postnatal periods has direct, distinct, and long-lasting consequences on social behaviour and metabolism, depending on the sex and on the timing of inactivation. Our results also demonstrate a role of foetal/neonate oxytocin neurons in the timing of birth and in early feeding behaviour. Health sciences/Diseases/Psychiatric disorders/Autism spectrum disorders Biological sciences/Neuroscience/Molecular neuroscience Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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