Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets

Abstract Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (...

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Main Authors: Valentine Turpin, Maud Schaffhauser, Mathieu Thabault, Agnès Aubert, Corinne Joffre, Eric Balado, Jean-Emmanuel Longueville, Maureen Francheteau, Christophe Burucoa, Maxime Pichon, Sophie Layé, Mohamed Jaber
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-38423-z
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author Valentine Turpin
Maud Schaffhauser
Mathieu Thabault
Agnès Aubert
Corinne Joffre
Eric Balado
Jean-Emmanuel Longueville
Maureen Francheteau
Christophe Burucoa
Maxime Pichon
Sophie Layé
Mohamed Jaber
author_facet Valentine Turpin
Maud Schaffhauser
Mathieu Thabault
Agnès Aubert
Corinne Joffre
Eric Balado
Jean-Emmanuel Longueville
Maureen Francheteau
Christophe Burucoa
Maxime Pichon
Sophie Layé
Mohamed Jaber
author_sort Valentine Turpin
collection DOAJ
description Abstract Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD.
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spelling doaj.art-5f3cf5c9513340918eb60617927349b72023-07-16T11:16:05ZengNature PortfolioScientific Reports2045-23222023-07-0113111410.1038/s41598-023-38423-zMice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched dietsValentine Turpin0Maud Schaffhauser1Mathieu Thabault2Agnès Aubert3Corinne Joffre4Eric Balado5Jean-Emmanuel Longueville6Maureen Francheteau7Christophe Burucoa8Maxime Pichon9Sophie Layé10Mohamed Jaber11Université de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Bordeaux, INRAE, Bordeaux INP, NutriNeurOUniversité de Bordeaux, INRAE, Bordeaux INP, NutriNeurOUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesUniversité de Poitiers, Inserm, PHAR2Université de Poitiers, Inserm, PHAR2Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurOUniversité de Poitiers, Inserm, Laboratoire de Neurosciences Expérimentales et CliniquesAbstract Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD.https://doi.org/10.1038/s41598-023-38423-z
spellingShingle Valentine Turpin
Maud Schaffhauser
Mathieu Thabault
Agnès Aubert
Corinne Joffre
Eric Balado
Jean-Emmanuel Longueville
Maureen Francheteau
Christophe Burucoa
Maxime Pichon
Sophie Layé
Mohamed Jaber
Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
Scientific Reports
title Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
title_full Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
title_fullStr Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
title_full_unstemmed Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
title_short Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets
title_sort mice prenatally exposed to valproic acid do not show autism related disorders when fed with polyunsaturated fatty acid enriched diets
url https://doi.org/10.1038/s41598-023-38423-z
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