Identifying the long-term effects of maternal immune activation in offspring
Abstract/Contents
- Abstract
- There is growing evidence that immune perturbations in the developing CNS can influence neurodevelopment and influence the individual's risk for CNS-related disorders throughout life. In particular, there is strong epidemiological evidence that maternal immune activation (MIA) during early to mid-gestation is associated with increased risk for neurodevelopmental disorders such as autism and schizophrenia in the offspring. However, the molecular mechanism of how MIA impacts neural function and behavior is still unclear. To tackle this challenge, our lab and others have developed mouse models to investigate MIA-induced phenotypes and elucidate the mechanisms by which an early event during pregnancy could induce lasting impacts on the offspring's neural outcomes. Here, we combined high dimensional transcriptional analysis with histological methods and behavioral assays to determine how changes in transcriptional and cellular profiles relate to functional consequences. Better understanding of the underlying mechanisms of how MIA predisposes an offspring to neurodevelopment and neuropsychiatric disorders could allow for targeted therapeutic interventions in the clinic. In this dissertation, I present work characterizing the mechanisms by which MIA influences both early neurodevelopment as well as responses to environmental and genetic insults later in life. In chapter 2, I demonstrate that MIA through TLR-3 versus TLR-4 signaling results in distinct placental and fetal outcomes during development. In chapter 3, I identify long-term transcriptional changes following prenatal immune challenges that subsequently impact neuroinflammatory responses in adulthood. In chapter 4, I elucidate how gene-environment interactions between ASD risk genes and MIA can exacerbate placental and neural phenotypes. Collectively, this dissertation thesis presents fundamental molecular insights into MIA mechanisms with the ultimate goal of understanding how prenatal immune challenges impact brain function and human health.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Su, Jennifer |
|---|---|
| Degree supervisor | Palmer, Theo |
| Thesis advisor | Palmer, Theo |
| Thesis advisor | Idoyaga, Juliana |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Wyss-Coray, Anton |
| Degree committee member | Idoyaga, Juliana |
| Degree committee member | Monje-Deisseroth, Michelle |
| Degree committee member | Wyss-Coray, Anton |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jennifer Su. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/cx510tj5979 |
Access conditions
- Copyright
- © 2022 by Jennifer Su
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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