Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder
Abstract
BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. METHODS: We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. RESULTS: Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. CONCLUSIONS: Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. Autism Res 2017, 10: 456-471. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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Ketogenic diet treatment of BTBR mice improved deficits related to myelin formation and white matter development/connectivity, acting on neurotransmitter signaling pathways including glutamate, serotonin, neuronal nitric acid synthase, and dopamine.
“KD treatment of BTBR mice also improved deficits typical of ASD related to myelin formation and white matter development/connectivity, acting on neurotransmitter signaling pathways including glutamate, serotonin, neuronal nitric acid synthase, and dopamine [109].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [109]
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Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions
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The Current Status of the Ketogenic Diet in Psychiatry
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- Authors
- Mychasiuk, R., & Rho, J. M.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Mychasiuk, Richelle
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2016-08-16
- Volume
- 10
- Issue
- 3
- Pages
- 456-471
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- OpenAlex
- W2515669969
- Cited by
- 45
- References
- 67
- Citations by year
- 2026: 2 · 2025: 5 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 3 · 2017: 5
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Lethbridge
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- autism spectrum disorder, ketogenic diet, gene expression, temporal cortex, hippocampus, stress response, myelination, white matter development, GABAergic neurotransmission, vitamin D pathway, cAMP signaling, therapeutic target
- MeSH terms
- Autism Spectrum Disorder, Animals, Brain, Disease Models, Animal, Humans, Male, Mice, Inbred Strains, RNA, Messenger, Gene Expression, Mice, Diet, Ketogenic
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