The Impact of Antenatal Dexamethasone Exposure on Neurodevelopment in Adolescent Male and Female Rats

• Grant number: 24/14414-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Gabriela Esteves Sbardellotto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glucocorticoids (GCs), like cortisol in humans, are steroid hormones essential for endocrine regulation and adaptation to stress. They interact with specific receptors, such as glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), affecting processes ranging from neuronal differentiation to mood control and cognition. Prenatal exposure to synthetic glucocorticoids, such as dexamethasone, can impair offspring neuronal development and lead to neuropsychiatric disorders. Furthermore, stress, defined as a state of challenge to homeostasis, can activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in an increase in cortisol levels. This situation is closely associated with conditions such as depression, panic disorder and anxiety. Emotional stimulation can modulate the learning process and memory formation. However, stress can also impair these functions, leading to long-term negative effects. Prenatal exposure to glucocorticoids can reduce neuronal cell proliferation and inhibit neurogenesis, affecting areas such as the hippocampus. Given the lack of drug substitutes for preventing risks related to prematurity, the use of synthetic glucocorticoids is still necessary. Therefore, it is important to better understand the Glucocorticoids (GCs), such as cortisol in humans, are steroid hormones essential for endocrine regulation and adaptation to stress. They interact with specific receptors, such as glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), affecting processes ranging from neuronal differentiation to mood control and cognition. Prenatal exposure to synthetic glucocorticoids, such as dexamethasone, can impair offspring's neuronal development and lead to neuropsychiatric disorders. Furthermore, stress, a state of challenge to homeostasis, can activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, increasing cortisol levels. This situation is closely associated with conditions such as depression, panic disorder, and anxiety. Emotional stimulation can modulate the learning process and memory formation. However, stress can also impair these functions, leading to long-term adverse effects. Prenatal exposure to glucocorticoids can reduce neuronal cell proliferation and inhibit neurogenesis, affecting areas such as the hippocampus. Given the lack of drug substitutes for preventing risks related to prematurity, the use of synthetic glucocorticoids is still necessary. Therefore, it is crucial to understand the effects of dexamethasone on neurodevelopment better, helping to implement public policies to ensure better monitoring and quality of life for individuals exposed to this medication in the prenatal period.