title: The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.
abstract: OBJECTIVE
  Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism.
  
  
  METHODS
  Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD).
  
  
  RESULTS
  When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice.
  
  
  CONCLUSIONS
  VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.
authors: a Translational Research Group in Autism Spectrum Disorder (GETTEA) , Porto Alegre , Brazil.|b Food and Nutrition Research Center , Hospital de Clínicas de Porto Alegre , Brazil.|c Postgraduate Program in Child and Adolescent Health , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors: Kamila
authors: K
authors: Castro
authors: a Translational Research Group in Autism Spectrum Disorder (GETTEA) , Porto Alegre , Brazil.|c Postgraduate Program in Child and Adolescent Health , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors: Diego
authors: D
authors: Baronio
authors: b Food and Nutrition Research Center , Hospital de Clínicas de Porto Alegre , Brazil.|d Postgraduate Program in Public Health, Academic Unit of Health Science , Universidade do Extremo Sul Catarinense , Criciúma , SC , Brazil.
authors: Ingrid Schweigert
authors: IS
authors: Perry
authors: a Translational Research Group in Autism Spectrum Disorder (GETTEA) , Porto Alegre , Brazil.|c Postgraduate Program in Child and Adolescent Health , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|e Child Neurology Unit, Hospital de Clínicas de Porto Alegre , Brazil.
authors: Rudimar Dos Santos
authors: RDS
authors: Riesgo
authors: a Translational Research Group in Autism Spectrum Disorder (GETTEA) , Porto Alegre , Brazil.
authors: Carmem
authors: C
authors: Gottfried
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control; D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006120:Grooming / Q000187:drug effects; D008297:Male; D051379:Mice; D017288:Pain Threshold / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: Autistic disorder; Ketogenic diet; Valproic acid