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

Publication date: Jul 11, 2023

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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Concepts Keywords
450mg Acid
Autism Asd
Cardinal Autism
Dietary Compared
Dysbiosis Diet


Type Source Name
drug DRUGBANK Dimercaprol
disease MESH autism spectrum disorder
disease MESH autism
drug DRUGBANK Valproic Acid
disease MESH dysbiosis
disease MESH gait
drug DRUGBANK Coenzyme M
drug DRUGBANK Etodolac
disease MESH neurodevelopmental disorder
disease MESH inflammation
pathway REACTOME Fatty acids
drug DRUGBANK Linoleic acid
drug DRUGBANK Alpha-Linolenic Acid
drug DRUGBANK Arachidonic Acid
drug DRUGBANK Icosapent
drug DRUGBANK Doconexent
disease MESH etiology
disease MESH defects
disease MESH syndromes
drug DRUGBANK Proline
drug DRUGBANK Trestolone
drug DRUGBANK L-Arginine
disease MESH weaning
drug DRUGBANK Isoxaflutole
drug DRUGBANK Water
drug DRUGBANK Pentobarbital
drug DRUGBANK Silicon dioxide
disease MESH Mental Disorders
disease MESH brain disease
drug DRUGBANK Omega-3 fatty acids
disease MESH attention deficit hyperactivity disorder
drug DRUGBANK Omega-6 fatty acids
drug DRUGBANK Cyanocobalamin
drug DRUGBANK Propanoic acid
drug DRUGBANK Donepezil
disease MESH cerebellar hypoplasia
disease MESH ataxia
drug DRUGBANK Dopamine
drug DRUGBANK Doxorubicin
disease MESH oxidative stress
disease MESH neuroinflammation
disease MESH cerebellar dysfunctions
drug DRUGBANK Ketamine
disease MESH endotoxemia
disease MESH influenza
drug DRUGBANK Etoperidone

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