Bioinformatics characterization of the molecular pathways impacted by immune challenges in the amygdala

Intrauterine environment during pregnancy plays a critical role in fetal development, and environmental stressors and pathogens that elicit an immune response in the mother have the ability to influence critical processes within the fetus during development. This maternal immune activation (MIA) can have lasting effects on the fetus and has been associated with neurological and behavioral deficits often seen in neurodevelopmental, neurodegenerative, and mood disorders. The amygdala, a structure located in the forebrain, plays a central role in many processes associated with these disorders, as well as an individual’s response to stressors. In these studies, high-throughput RNA sequencing along with bioinformatics approaches were used to characterize the transcriptomic changes in the amygdala of pigs subject to viral-elicited MIA compared to control pigs. We investigated how the amygdalar transcriptome between MIA and control pigs was altered with respect to sex; in the presence of a second, post-natal stressor; and how transcripts were differentially alternatively spliced between MIA and control pigs within sex. Functional enrichment analysis provided insight into affected pathways, while protein-protein interaction networks identified non-canonical relationships impacted by MIA. Additionally, complementary analyses, such as transcription factor enrichment analysis, which was performed to investigate the interaction between MIA and a post-natal stressor (i.e. weaning) aided in identifying shared transcription factors among dysregulated genes. Our approaches revealed lasting and sex-dependent changes to the transcriptome of the amygdala following MIA, altered transcription in the amygdala in response to weaning stress following MIA, and aberrant alternative splicing in the amygdala of both male and female pigs exposed to MIA. Investigation of the affected genes and pathways involved confirmed the link between MIA and neurological and behavioral disorders.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Keever-Keigher, Marissa Rachel

Contributors dc:contributor

• Rodriguez-Zas, Sandra L
• Caetano-Anolles, Gustavo
• Wheeler, Matthew B
• Villamil, Maria B

• Maternal Immune Activation
• RNA-seq
• Amygdala
• Pig

Statement dc:rights

• Copyright 2021 Marissa Keever-Keigher

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/113243

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/113243