Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation

Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflamma...

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Main Authors: Chiara Cipriani, Anna Maria Tartaglione, Martina Giudice, Erica D’Avorio, Vita Petrone, Nicola Toschi, Flavia Chiarotti, Martino Tony Miele, Gemma Calamandrei, Enrico Garaci, Claudia Matteucci, Paola Sinibaldi-Vallebona, Laura Ricceri, Emanuela Balestrieri
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/22/13930
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author Chiara Cipriani
Anna Maria Tartaglione
Martina Giudice
Erica D’Avorio
Vita Petrone
Nicola Toschi
Flavia Chiarotti
Martino Tony Miele
Gemma Calamandrei
Enrico Garaci
Claudia Matteucci
Paola Sinibaldi-Vallebona
Laura Ricceri
Emanuela Balestrieri
author_facet Chiara Cipriani
Anna Maria Tartaglione
Martina Giudice
Erica D’Avorio
Vita Petrone
Nicola Toschi
Flavia Chiarotti
Martino Tony Miele
Gemma Calamandrei
Enrico Garaci
Claudia Matteucci
Paola Sinibaldi-Vallebona
Laura Ricceri
Emanuela Balestrieri
author_sort Chiara Cipriani
collection DOAJ
description Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflammatory profiles, with an increase in pro-inflammatory cytokines and microglial markers. In addition to neuroinflammatory response, an abnormal expression of endogenous retroviruses (ERVs) has been identified in neurodevelopmental disorders and have been found to correlate with disease severity. Our aim was to evaluate the transcriptional profile of several ERV families, ERV-related genes, and inflammatory mediators (by RT real-time PCR) in mouse offspring of both sexes, prenatally exposed to polyinosinic:polycytidylic acid (Poly I:C), a synthetic double-stranded RNA molecule targeting TLR-3 that mimics viral maternal infection during pregnancy. We found that prenatal exposure to Poly I:C deregulated the expression of some ERVs and ERV-related genes both in the prefrontal cortex (PFC) and hippocampus, while no changes were detected in the blood. Interestingly, sex-related differences in the expression levels of some ERVs, ERV-related genes, and inflammatory mediators that were higher in females than in males emerged only in PFC. Our findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.
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spelling doaj.art-8fa4167853bd4cf9866d3f10a973e69c2023-11-24T08:35:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221393010.3390/ijms232213930Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune ActivationChiara Cipriani0Anna Maria Tartaglione1Martina Giudice2Erica D’Avorio3Vita Petrone4Nicola Toschi5Flavia Chiarotti6Martino Tony Miele7Gemma Calamandrei8Enrico Garaci9Claudia Matteucci10Paola Sinibaldi-Vallebona11Laura Ricceri12Emanuela Balestrieri13Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), 00161 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, ItalyCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), 00161 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), 00161 Rome, ItalyUniversity San Raffaele, 00166 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), 00161 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyMaternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflammatory profiles, with an increase in pro-inflammatory cytokines and microglial markers. In addition to neuroinflammatory response, an abnormal expression of endogenous retroviruses (ERVs) has been identified in neurodevelopmental disorders and have been found to correlate with disease severity. Our aim was to evaluate the transcriptional profile of several ERV families, ERV-related genes, and inflammatory mediators (by RT real-time PCR) in mouse offspring of both sexes, prenatally exposed to polyinosinic:polycytidylic acid (Poly I:C), a synthetic double-stranded RNA molecule targeting TLR-3 that mimics viral maternal infection during pregnancy. We found that prenatal exposure to Poly I:C deregulated the expression of some ERVs and ERV-related genes both in the prefrontal cortex (PFC) and hippocampus, while no changes were detected in the blood. Interestingly, sex-related differences in the expression levels of some ERVs, ERV-related genes, and inflammatory mediators that were higher in females than in males emerged only in PFC. Our findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.https://www.mdpi.com/1422-0067/23/22/13930endogenous retroviruses (ERVs)autism spectrum disordersocial behaviorPoly I:Ccytokinesneuroinflammation
spellingShingle Chiara Cipriani
Anna Maria Tartaglione
Martina Giudice
Erica D’Avorio
Vita Petrone
Nicola Toschi
Flavia Chiarotti
Martino Tony Miele
Gemma Calamandrei
Enrico Garaci
Claudia Matteucci
Paola Sinibaldi-Vallebona
Laura Ricceri
Emanuela Balestrieri
Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
International Journal of Molecular Sciences
endogenous retroviruses (ERVs)
autism spectrum disorder
social behavior
Poly I:C
cytokines
neuroinflammation
title Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
title_full Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
title_fullStr Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
title_full_unstemmed Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
title_short Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation
title_sort differential expression of endogenous retroviruses and inflammatory mediators in female and male offspring in a mouse model of maternal immune activation
topic endogenous retroviruses (ERVs)
autism spectrum disorder
social behavior
Poly I:C
cytokines
neuroinflammation
url https://www.mdpi.com/1422-0067/23/22/13930
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