Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally
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 sympt...
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Molecular Autism |
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| Online Access: | http://link.springer.com/article/10.1186/s13229-017-0160-x |
| _version_ | 1828942705916379136 |
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| author | Catherine E. Barrett Thomas M. Hennessey Katelyn M. Gordon Steve J. Ryan Morgan L. McNair Kerry J. Ressler Donald G. Rainnie |
| author_facet | Catherine E. Barrett Thomas M. Hennessey Katelyn M. Gordon Steve J. Ryan Morgan L. McNair Kerry J. Ressler Donald G. Rainnie |
| author_sort | Catherine E. Barrett |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T04:00:27Z |
| format | Article |
| id | doaj.art-23e70fc8442f40efa8b76b2e593a9932 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-14T04:00:27Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-23e70fc8442f40efa8b76b2e593a99322022-12-21T23:17:57ZengBMCMolecular Autism2040-23922017-08-018111710.1186/s13229-017-0160-xDevelopmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatallyCatherine E. Barrett0Thomas M. Hennessey1Katelyn M. Gordon2Steve J. Ryan3Morgan L. McNair4Kerry J. Ressler5Donald G. Rainnie6Silvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversitySilvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversitySilvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversitySilvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversitySilvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversityDepartment of Psychiatry, McLean Hospital, Harvard Medical SchoolSilvio O. Conte Center for Oxytocin and Social Cognition, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Emory UniversityAbstract 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.http://link.springer.com/article/10.1186/s13229-017-0160-xValproic acidAutismSocial behaviorBasolateral amygdalaProtein kinase ATranscriptomics |
| spellingShingle | Catherine E. Barrett Thomas M. Hennessey Katelyn M. Gordon Steve J. Ryan Morgan L. McNair Kerry J. Ressler Donald G. Rainnie Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally Molecular Autism Valproic acid Autism Social behavior Basolateral amygdala Protein kinase A Transcriptomics |
| title | Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| title_full | Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| title_fullStr | Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| title_full_unstemmed | Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| title_short | Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| title_sort | developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally |
| topic | Valproic acid Autism Social behavior Basolateral amygdala Protein kinase A Transcriptomics |
| url | http://link.springer.com/article/10.1186/s13229-017-0160-x |
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