Understanding peripheral and brain changes in a double hit model

Rymut, Haley Elizabeth

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https://hdl.handle.net/2142/115724 Copy

Description

Title

Understanding peripheral and brain changes in a double hit model

Author(s)

Rymut, Haley Elizabeth

Issue Date

2022-04-22

Director of Research (if dissertation) or Advisor (if thesis)

Rodriguez-Zas, Sandra

Doctoral Committee Chair(s)

Rodriguez-Zas, Sandra

Committee Member(s)

• Villamil, Maria
• Caetano-Anolles, Gustavo
• Wheeler, Matthew

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• maternal immune activation
• PRRSV
• cytokines
• biomarkers
• hippocampus
• transcriptome
• double hit hypothesis

Abstract

The combined effects of maternal immune activation (MIA), a second stress later in life, and sex have not been fully documented in pigs. Deciphering the physiological and transcriptomic effects of MIA and a second stress is especially relevant in diseases that alter fetal development. Three studies advanced the understanding of the effects of MIA and a second stress on biochemical and immune markers and gene expression in female and male pigs. In the first study, male and female pigs were weaned at 21 days of age, and the effects of weaning stress in combination with MIA were analyzed on blood indicators of organ performance and inflammation. Weaning effects on anion gap and bilirubin levels were lower among MIA pigs, suggesting a weaning stress tolerance due to MIA. The levels of cytokines interleukin 1β, interleukin 2, and interleukin 6 were highest in weaned MIA females. In the second study, blood indicators were profiled in 60-day-old pigs exposed to MIA, while the second challenge included an inflammatory challenge or fasting. While cholesterol levels suggest that prenatal MIA stress may sensitize pigs to postnatal stressors, BUN levels suggest that MIA may prime the pigs to be more tolerant to postnatal stressors. Postnatal immune challenge heightened the levels of interferon gamma and interleukin 8. The third study used RNA-sequencing to investigate the effects of weaning, MIA, and sex on gene expression in the hippocampus of 22-day old pigs. Overall, 574 genes across 17 neurological and immune pathways were differentially expressed across factor levels. The expression patterns in the terpenoid synthesis pathway indicate that MIA and weaning stress impact females more intensely. Gene over-expression was associated with MIA in neurological development pathways. Our findings offer insights into the impact of MIA and second stressors on peripheral and brain molecular profiles associated with growth and behavior.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Haley Rymut

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