Altered expression levels of neurodevelopmental proteins in fetal brains of BTBR T+tf/J mice with autism-like behavioral characteristics

J Toxicol Environ Health A. 2015;78(8):516-23. doi: 10.1080/15287394.2015.1010466.

Abstract

Autism is a brain developmental disorder with characteristics of social interaction defects, language and communication dysfunction, and repetitive behavior. Occurrence of autism is continuously increasing, but the cause of autism is not clearly defined. Genetic linkage or environmental factors were proposed as sources for pathogenesis of autism. BTBR T+tf/J (BTBR) mice were reported as an appropriate animal model for autism investigation because of their similarities in behavioral abnormalities with human autistic subjects. The aim of this study was to evaluate expression levels of proteins involved with brain development at fetal stage of BTBR mice. FVB/NJ mice were used as a control strain because of their social behaviors. Level of fetal brain immunoglobulin (Ig) G deposit was also evaluated. Fetal brains were obtained at d 18 of gestational period. Thirty-one and 27 fetuses were obtained from 3 pregnant BTBR and FVB dams, respectively. The level of glial fibrillary acidic protein expression was significantly lower in fetal brains of BTBR than FVB/NJ mice. Expression of brain-derived neurotrophic factor and myelin basic protein was significantly more upregulated in BTBR than in FVB/NJ mice. No significant difference was obtained for nerve growth factor between the two strains. Levels of IgG isotypes deposited in fetal brain of BTBR mice were significantly higher than in FVB mice except for IgG1. Overall, these results suggest that prenatal alterations in expression of various fetal brain proteins may be implicated in aberrant behavioral characteristics of BTBR mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / immunology
  • Autistic Disorder / metabolism*
  • Autoantibodies / genetics
  • Autoantibodies / metabolism
  • Behavior, Animal
  • Brain / embryology
  • Brain / immunology
  • Brain / metabolism*
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Female
  • Fetal Development
  • Gene Expression Regulation, Developmental*
  • Germ-Free Life
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism*
  • Neurogenesis*
  • Neuroglia / immunology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / immunology
  • Neurons / metabolism
  • Neurons / pathology
  • Pregnancy

Substances

  • Autoantibodies
  • Brain-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Immunoglobulin G
  • Mbp protein, mouse
  • Myelin Basic Protein