title: Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/Jmouse 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.
authors.affiliation: Departments of Psychology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Richelle
authors.initials: R
authors.lastname: Mychasiuk
authors.affiliation: Departments of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D055423:Diet, Ketogenic / Q000379:methods*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger
keywords: RNAseq; autism spectrum disorder; development; hippocampus; ketogenic diet; mitochondria; temporal cortex