Stress during pregnancy leads to long-term consequences in the offspring
Date
2024
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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.
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Subject
neuroendocrine
neurovascular
stress
neuropsychiatric disorders
maternal stress
sex differences