Dendritic spine anomalies and PTEN alterations in a mouse model of VPA-induced autism spectrum disorder

Usman Mahmood, Sangzin Ahn, Eun-Jeong Yang, Moonseok Choi, Hyunju Kim, Philip Regan, Kwangwook Cho, Hye-Sun Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although the precise molecular and cellular links remain ill-defined. In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD. A mouse model was established by injecting VPA at embryonic day 13, and its behavioral phenotypes including impaired social interaction, increased repetitive behaviors and decreased nociception were observed at postnatal days 21-42. VPA-treated mice showed dysregulation of synaptic structure in cortical neurons, including a reduced proportion of filopodium-type and stubby spines and increased proportions of thin and mushroom-type spines, along with a decreased spine head size. We also found that VPA-treatment led to decreased expression of phosphate and tensin homolog (PTEN) and increased levels of p-AKT protein in the hippocampus and cortex. Our data suggest that there is a correlation between VPA exposure and dysregulation of PTEN with ASD-like behavioral and neuroanatomical changes, and this may be a potential mechanism of VPA-induced ASD.

Original languageEnglish
Pages (from-to)110-121
Number of pages12
JournalPulmonary Pharmacology & Therapeutics
Volume128
Early online date18 Aug 2017
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Animals
  • Autism Spectrum Disorder/chemically induced
  • Behavior, Animal/drug effects
  • Cerebral Cortex/drug effects
  • Dendritic Spines/drug effects
  • Disease Models, Animal
  • Female
  • Hippocampus/drug effects
  • Male
  • Mice, Inbred BALB C
  • PTEN Phosphohydrolase/metabolism
  • Pregnancy
  • Proto-Oncogene Proteins c-akt/metabolism
  • Valproic Acid

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