Aberrant Mitochondrial Morphology and Function in the BTBR Mouse Model of Autism Is Improved by Two Weeks of Ketogenic Diet
| Autor: | Timothy E. Shutt, Rasha Sabouny, Nellie C. Yee, Jong M. Rho, Golam M. Uddin, Bianca R. Villa, Richelle Mychasiuk, Younghee Ahn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
fusion
Ketogenic Bioenergetics Autism Spectrum Disorder Autism medicine.medical_treatment Mitochondrion Mitochondrial Dynamics lcsh:Chemistry Mice Neurodevelopmental disorder 2.1 Biological and endogenous factors lcsh:QH301-705.5 Spectroscopy Neurons Pediatric Disease Management General Medicine Mitochondria Computer Science Applications mitochondria Mental Health Autism spectrum disorder ketogenic diet Phosphorylation Disease Susceptibility Diet Ketogenic medicine.medical_specialty Intellectual and Developmental Disabilities (IDD) autism spectrum disorder Biology BTBR mouse Article Catalysis Mitochondrial Proteins Inorganic Chemistry mitochondrial function Internal medicine Behavioral and Social Science Complementary and Integrative Health mental disorders Genetics medicine Animals fission Physical and Theoretical Chemistry Molecular Biology Nutrition Chemical Physics Animal Organic Chemistry Neurosciences medicine.disease mitochondrial dynamics Diet Brain Disorders Disease Models Animal Endocrinology lcsh:Biology (General) lcsh:QD1-999 Disease Models Other Biological Sciences Other Chemical Sciences Biomarkers Function (biology) Ketogenic diet |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 9 International journal of molecular sciences, vol 21, iss 9 International Journal of Molecular Sciences, Vol 21, Iss 3266, p 3266 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21093266 |
| Popis: | Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder that exhibits a common set of behavioral and cognitive impairments. Although the etiology of ASD remains unclear, mitochondrial dysfunction has recently emerged as a possible causative factor underlying ASD. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that augments mitochondrial function, and has been shown to reduce autistic behaviors in both humans and in rodent models of ASD. The aim of the current study was to examine mitochondrial bioenergetics in the BTBR mouse model of ASD and to determine whether the KD improves mitochondrial function. We also investigated changes in mitochondrial morphology, which can directly influence mitochondrial function. We found that BTBR mice had altered mitochondrial function and exhibited smaller more fragmented mitochondria compared to C57BL/6J controls, and that supplementation with the KD improved both mitochondrial function and morphology. We also identified activating phosphorylation of two fission proteins, pDRP1S616 and pMFFS146, in BTBR mice, consistent with the increased mitochondrial fragmentation that we observed. Intriguingly, we found that the KD decreased pDRP1S616 levels in BTBR mice, likely contributing to the restoration of mitochondrial morphology. Overall, these data suggest that impaired mitochondrial bioenergetics and mitochondrial fragmentation may contribute to the etiology of ASD and that these alterations can be reversed with KD treatment. |
| Databáze: | OpenAIRE |
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