Document Type

Article

Department

​Neuroscience

Publication Date

2017

Abstract

Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.

Comments

Published under Open Access terms and a Creative Commons license as

David N. Ruskin, Michelle I. Murphy ’14, Sierra L. Slade ’15, Susan A. Masino. “Ketogenic Diet Improves Behaviors in a Maternal Immune Activation Model of Autism Spectrum Disorder.” PLoS ONE 12 (January 2017): e0171643.

https://doi.org/10.1371/journal.pone.0171643

Michelle Murphy and Sierra Slade were students at Trinity College, Hartford Connecticut at time of publication.

Publication Title

PLoS ONE

Volume

12

DOI

10.1371/journal.pone.0171643

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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Neurosciences Commons

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