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Updated: Jun 11, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic
F I Roullet1, L Wollaston, D Decatanzaro
1Department of Psychiatry and Behavioural Neurosciences, McMaster University, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6 - Canada.
Insights
Maternal valproic acid (VPA) exposure in mice caused developmental delays, impaired social behaviors, and altered brain gene expression, supporting its use as an autism model. This research highlights potential genetic links to autism spectrum disorder.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Maternal exposure to valproic acid (VPA) in rodents and humans is linked to adverse neurological and behavioral outcomes, including autism spectrum disorder (ASD).
- Understanding the mechanisms underlying VPA's effects is crucial for developing preventative or therapeutic strategies for ASD.
Purpose of the Study:
- To investigate the impact of prenatal valproic acid (VPA) exposure on physical development, sensory processing, social behavior, and gene expression in mouse pups.
- To evaluate the utility of the VPA-exposed mouse model for studying human autism.
Main Methods:
- Mouse pups were exposed to VPA in utero.
- Evaluated physical development, olfactory discrimination, and pre-weaning social behaviors.
- Measured cortical expression of plasticity-related genes, including brain-derived neurotrophic factor (BDNF) and NMDA receptor subunits (NR2A, NR2B) using in situ hybridization.
Main Results:
- VPA-exposed mouse pups exhibited delayed physical development, impaired olfactory discrimination, and dysfunctional social behaviors.
- Cortical expression of BDNF mRNA was significantly lower in VPA-exposed mice compared to controls.
- Alterations in NR2A and NR2B NMDA receptor subunit expression were also observed (data not detailed in abstract).
Conclusions:
- Prenatal VPA exposure in mice leads to significant deficits in development, sensory processing, and social behavior, mirroring aspects of human fetal valproate syndrome and autism.
- Reduced expression of BDNF and altered NMDA receptor subunits in the cortex suggest that disruptions in plasticity-related genes may underlie the observed behavioral phenotype.
- The VPA mouse model is validated as a relevant tool for investigating the neurobiological underpinnings of autism spectrum disorder.
Abstract:
Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development. In humans, prenatal exposure to VPA can induce fetal valproate syndrome, which has been associated with autism. The present study examined mouse pups exposed in utero to VPA, measuring physical development, olfactory discrimination, and social behavior as well as expression of plasticity-related genes, brain derived neurotrophic factor (BDNF) and NMDA receptor subunits NR2A and NR2B. VPA-exposed mice showed delayed physical development, impaired olfactory discrimination, and dysfunctional pre-weaning social behavior. In situ hybridization experiments revealed lower cortical expression of BDNF mRNA in VPA animals. These results support the validity of the VPA mouse model for human autism and suggest that alterations in plasticity-related genes may contribute to the behavioral phenotype.
