Transcriptional and splicing dysregulation in the prefrontal cortex in valproic acid rat model of autism

Reprod Toxicol. 2018 Apr:77:53-61. doi: 10.1016/j.reprotox.2018.01.008. Epub 2018 Feb 7.

Abstract

Gene-environmental interaction could be the major cause of autism. The aim of the current study is to detect the effects of valproic acid on gene expression profiles and alternatively spliced genes in the prefrontal cortex in rat models of autism. Female rats received a single intraperitoneal injection of 600 mg/kg valproic acid at day 12.5 post-conception, and controls were injected with saline. Only male offspring were employed in the current study. RNA sequencing was used to investigate transcriptome in the prefrontal cortex of VPA-exposed rats. There were 3228 differently expressed genes and 637 alternative spliced genes, in VPA rats compared to controls. Pathways enrichment among the differently expressed genes and alternatively spliced genes were associated with neurological diseases and neural system development. The results implied VPA affected transcriptional and splicing events genome-wide and the transcriptional and splicing events may be associated with the autistic behaviors of VPA rats.

Keywords: Alternative splicing gene; Autism; RNA sequencing (RNA-seq); Transcriptome; Valproic acid (VPA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects*
  • Animals
  • Anticonvulsants / toxicity*
  • Autistic Disorder / chemically induced*
  • Autistic Disorder / genetics*
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Female
  • Male
  • Maternal-Fetal Exchange
  • Prefrontal Cortex / metabolism*
  • Pregnancy
  • Rats, Sprague-Dawley
  • Smell / drug effects
  • Social Behavior
  • Swimming
  • Transcription, Genetic / drug effects*
  • Transcriptome / drug effects
  • Valproic Acid / toxicity*

Substances

  • Anticonvulsants
  • Valproic Acid