Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation
The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Immuno |
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| Online Access: | https://www.mdpi.com/2673-5601/1/4/35 |
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| author | Bruce R. Southey Marissa R. Keever-Keigher Haley E. Rymut Laurie A. Rund Rodney W. Johnson Sandra L. Rodriguez-Zas |
| author_facet | Bruce R. Southey Marissa R. Keever-Keigher Haley E. Rymut Laurie A. Rund Rodney W. Johnson Sandra L. Rodriguez-Zas |
| author_sort | Bruce R. Southey |
| collection | DOAJ |
| description | The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted <i>p</i>-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted <i>p</i>-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles. |
| first_indexed | 2024-03-10T03:53:58Z |
| format | Article |
| id | doaj.art-b9237eb8c4524cf59e6f9be01964f50c |
| institution | Directory Open Access Journal |
| issn | 2673-5601 |
| language | English |
| last_indexed | 2024-03-10T03:53:58Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Immuno |
| spelling | doaj.art-b9237eb8c4524cf59e6f9be01964f50c2023-11-23T08:50:46ZengMDPI AGImmuno2673-56012021-11-011449951710.3390/immuno1040035Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune ActivationBruce R. Southey0Marissa R. Keever-Keigher1Haley E. Rymut2Laurie A. Rund3Rodney W. Johnson4Sandra L. Rodriguez-Zas5Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USAThe inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted <i>p</i>-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted <i>p</i>-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.https://www.mdpi.com/2673-5601/1/4/35alternative splicingmaternal immune activationweaning stresssexneurodevelopmental disorder |
| spellingShingle | Bruce R. Southey Marissa R. Keever-Keigher Haley E. Rymut Laurie A. Rund Rodney W. Johnson Sandra L. Rodriguez-Zas Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation Immuno alternative splicing maternal immune activation weaning stress sex neurodevelopmental disorder |
| title | Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation |
| title_full | Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation |
| title_fullStr | Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation |
| title_full_unstemmed | Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation |
| title_short | Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation |
| title_sort | disruption of alternative splicing in the amygdala of pigs exposed to maternal immune activation |
| topic | alternative splicing maternal immune activation weaning stress sex neurodevelopmental disorder |
| url | https://www.mdpi.com/2673-5601/1/4/35 |
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