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Molecular Autism
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Research

Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally

Authors: Catherine E. Barrett, Thomas M. Hennessey, Katelyn M. Gordon, Steve J. Ryan, Morgan L. McNair, Kerry J. Ressler, Donald G. Rainnie

Published in: Molecular Autism | Issue 1/2017

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Abstract

Background

The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD.

Methods

Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development.

Results

Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed.

Conclusions

As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.
Appendix
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Metadata
Title
Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally
Authors
Catherine E. Barrett
Thomas M. Hennessey
Katelyn M. Gordon
Steve J. Ryan
Morgan L. McNair
Kerry J. Ressler
Donald G. Rainnie
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0160-x

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Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study

Short report

The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis

Research

Balanced bifrontal transcranial direct current stimulation enhances working memory in adults with high-functioning autism: a sham-controlled crossover study

Short report

Initial evidence that non-clinical autistic traits are associated with lower income

Review

Bio-collections in autism research

Research

Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism