Stress during pregnancy leads to long-term consequences in the offspring
| dc.contributor.author | Sheng, Julietta Angelina, author | |
| dc.contributor.author | Tobet, Stuart, advisor | |
| dc.contributor.author | Smith, Bret, advisor | |
| dc.contributor.author | Myers, Brent, committee member | |
| dc.contributor.author | Hale, Taben, committee member | |
| dc.contributor.author | Chanda, Soham, committee member | |
| dc.date.accessioned | 2024-05-27T10:32:57Z | |
| dc.date.available | 2024-05-27T10:32:57Z | |
| dc.date.issued | 2024 | |
| dc.description.abstract | Neuropsychiatric disorders encompass a wide range of conditions that affect neurological health and brain function and lead to disabilities worldwide. Such disorders include, but are not limited to, Major Depressive Disorder, schizophrenia, and anxiety disorders. Risk factors for developing neuropsychiatric disorders are multifaceted and can range from genetic predisposition, lifestyle, and environmental influences. Exposure to maternal stress is one type of environmental factor that can lead to changes in brain function and signaling pathways and increase susceptibility for related diseases. Maternal stress encompasses a diverse array of environmental stimuli, ranging from acute traumatic events to chronic or day-to-day life stressors. Maternal stressors, experienced by pregnant women, lead to overexposure of stress hormones in the developing fetus and impact short- and long-term neurological health the offspring. These studies evaluated developmental, neuroendocrine, and behavioral outcomes in offspring exposed to different models of maternal stress. Chapter 1 provided a brief history of stress, the development of the hypothalamic-pituitary-adrenal axis that regulates the stress response, and maternal-fetal interactions in stress regulatory systems and related behaviors. Chapter 2 evaluated several models of maternal stress, maternal high fat diet, maternal caloric restriction, maternal exposure to synthetic glucocorticoids. Although there were vast discrepancies between each type of maternal stress, one similarity was an activated immune response with elevated maternal cytokines. Therefore, Chapter 3 characterized a model of maternal immune activation using a toll-like receptor agonist, Resiquimod, that increased maternal and fetal cytokines, produced delayed developmental milestones and stress-related behavioral impairments in prepubertal (social-like) and adult (social-like, depressive-like, anxiety-like) offspring. Because these behavioral phenotypes are partially regulated by the paraventricular nucleus of the hypothalamus (PVN), Chapter 4 examined the neuroendocrine stress response and blood-brain barrier of the PVN. Data showed altered stress response accompanied by impaired blood-brain barrier integrity in the PVN of the adult offspring exposed to maternal injection of Resiquimod. Taken together, Chapters 2, 3, and 4 suggest maternal stress led to negative developmental, behavioral, and cellular pathologies indicative of neuropsychiatric-like disease. By teasing apart these specific programming mechanisms, we can better diagnose and treat progression of neuro-related disorders. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | Sheng_colostate_0053A_18356.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/238529 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2020- | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | neuroendocrine | |
| dc.subject | neurovascular | |
| dc.subject | stress | |
| dc.subject | neuropsychiatric disorders | |
| dc.subject | maternal stress | |
| dc.subject | sex differences | |
| dc.title | Stress during pregnancy leads to long-term consequences in the offspring | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Biomedical Sciences | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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