Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid

F. I. Roullet; L. Wollaston; D. deCatanzaro; J. A. Foster

doi:10.1016/j.neuroscience.2010.06.069

Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid

F. I. Roullet, L. Wollaston, D. deCatanzaro, J. A. Foster

Research output: Contribution to journal › Article › peer-review

156 Scopus citations

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.

Original language	English (US)
Pages (from-to)	514-522
Number of pages	9
Journal	Neuroscience
Volume	170
Issue number	2
DOIs	https://doi.org/10.1016/j.neuroscience.2010.06.069
State	Published - Oct 13 2010
Externally published	Yes

Keywords

Brain derived neurotrophic factor
Gene expression
In situ hybridization
Social behavior
Valproic acid

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuroscience.2010.06.069

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title = "Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid",

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.",

keywords = "Brain derived neurotrophic factor, Gene expression, In situ hybridization, Social behavior, Valproic acid",

author = "Roullet, {F. I.} and L. Wollaston and D. deCatanzaro and Foster, {J. A.}",

note = "Funding Information: This research was supported by grants from the Natural Sciences and Engineering Research Council of Canada awarded to Jane Foster and Denys deCatanzaro. Florence I. Roullet was a recipient of the Father Sean O'Sullivan Research Centre postdoctoral fellowship and the Autism Research Training program. Lori Wollaston is a recipient of the Autism Research Training program.",

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doi = "10.1016/j.neuroscience.2010.06.069",

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AU - Wollaston, L.

AU - deCatanzaro, D.

AU - Foster, J. A.

N1 - Funding Information: This research was supported by grants from the Natural Sciences and Engineering Research Council of Canada awarded to Jane Foster and Denys deCatanzaro. Florence I. Roullet was a recipient of the Father Sean O'Sullivan Research Centre postdoctoral fellowship and the Autism Research Training program. Lori Wollaston is a recipient of the Autism Research Training program.

PY - 2010/10/13

Y1 - 2010/10/13

N2 - 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.

AB - 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.

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KW - Gene expression

KW - In situ hybridization

KW - Social behavior

KW - Valproic acid

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Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid

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Keywords

ASJC Scopus subject areas

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