VPA-induced apoptosis and behavioral deficits in neonatal mice

Brain Res. 2008 Apr 8;1203:126-32. doi: 10.1016/j.brainres.2008.01.055. Epub 2008 Feb 5.


Sodium valproate (VPA) administered to neonatal mice causes cognitive and motor deficits similar to those observed in humans with autism. In an effort to further evaluate similarities between early VPA exposure and autism, the present study examined treated mice for deficits in social behavior and neuronal damage. BALB/c mice injected on P14 with 400 mg/kg VPA engaged in fewer social interactions (including ano-genital sniffs, allogrooming, and crawl-under/over behaviors) than control mice. Treated mice also exhibited reduced motor activity in a social context but were not significantly different from controls when motor activity was assessed in non-social settings. A second set of BALB/c mice were treated with VPA on P14 and sacrificed at different times thereafter for histopathological analysis. At time-points 12 and 24 h following VPA, treated mice had up to a 30-fold increase in the number of TUNEL-positive cells in the external granule cell layer of the cerebellum and a 10-fold increase in TUNEL-positive cells in the dentate gyrus of the hippocampus. These observations may provide a histopathological correlate for the social deficits observed following post-natal VPA exposure and supports the use of early VPA administration as an animal model for the study of autism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Anticonvulsants / toxicity*
  • Apoptosis / drug effects*
  • Behavior, Animal / drug effects
  • Behavioral Symptoms / chemically induced*
  • Behavioral Symptoms / pathology*
  • Brain / drug effects
  • Brain / pathology
  • Cell Count
  • Female
  • In Situ Nick-End Labeling / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Sex Factors
  • Social Behavior
  • Time Factors
  • Valproic Acid / toxicity*


  • Anticonvulsants
  • Valproic Acid