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Author Notes:

Correspondence: Catherine E. Barrett, Phone: 404 727-3981, Email: cbarrett27@gmail.com

CB, TH, KG, and SR collected behavioral data and tissue samples.

MM analyzed ultrasonic vocalization data. CB and TH analyzed behavioral, transcriptomic, and proteomic data.

DR, KR, and CB designed the study.

All authors read, edited, and approved the final manuscript.

We are thankful to Gregory Tharp and Nirav Patel at the Yerkes Nonhuman Primate Genomics Core and to Duc Duong at the Emory Integrated Proteomics Core for carrying out RNA sequencing, LC-MS/MS, and assisting with statistical analyses.

We are also grateful to the animal care and veterinary staff at the Yerkes National Primate Research Center.

All protocols strictly conformed to the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health and were approved by the Emory University Institutional Animal Care and Use Committee.

The authors declare that they have no competing interests.

Subjects:

Research Funding:

This work was funded from an NIH Silvio O. Conte grant 1P50MH100023 and the National Primate Research Center base grant NIH OD P51OD11132.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • Neurosciences
  • Neurosciences & Neurology
  • Valproic acid
  • Autism
  • Social behavior
  • Basolateral amygdala
  • Protein kinase A
  • Transcriptomics
  • Proteomics
  • RNA sequencing
  • AUTISM SPECTRUM DISORDER
  • HIGH-FUNCTIONING AUTISM
  • BASOLATERAL AMYGDALA
  • GENE-EXPRESSION
  • ANIMAL-MODEL
  • IN-UTERO
  • SYNAPTIC PLASTICITY
  • PREFRONTAL CORTEX
  • ANXIETY DISORDERS
  • FEAR MEMORIES

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

Tools:

Journal Title:

Molecular Autism

Volume:

Volume 8

Publisher:

, Pages 42-42

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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