Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model

Int J Dev Neurosci. 2015 Aug:44:14-21. doi: 10.1016/j.ijdevneu.2015.04.350. Epub 2015 Apr 24.

Abstract

To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Δ5-desaturase, Δ6-desaturase and elongase (Elovl2), in VPA-exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism-like behavioral changes, the abnormal expression of apoptosis-related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down-regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.

Keywords: Animal model; Autism; Desaturases; Polyunsaturated fatty acids; Sexual dimorphism; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Animals
  • Anticonvulsants / toxicity*
  • Autistic Disorder / blood*
  • Autistic Disorder / chemically induced*
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acid Elongases
  • Fatty Acids, Unsaturated / blood*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / physiopathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Sex Factors
  • Valproic Acid / toxicity*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticonvulsants
  • Fatty Acids, Unsaturated
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Valproic Acid
  • Fatty Acid Desaturases
  • Acetyltransferases
  • Fatty Acid Elongases
  • Caspase 3