EXPOSURE TO STRESS EARLY IN LIFE AND ENHANCED RISK TO DEVELOP MOOD AND METABOLIC DISORDERS LATER IN LIFE: IDENTIFICATION OF THE COMMON PERIPHERAL AND CENTRAL MECHANISMS
type: CreativeWork
description: The intricate relationship between mental and physical health, particularly the co-occurrence of psychiatric disorders and metabolic conditions, has become a focus of recent research. Early-life stress (ELS) is recognized as a key factor that heightens the risk of developing mood and metabolic disorders, often resulting in comorbidities during adolescence and adulthood. This study investigates the role of ELS in contributing to psycho-metabolic comorbidities, with a focus on disruptions in the brain-liver axis, which is crucial for regulating metabolic and inflammatory processes. Using a rat model of prenatal stress (PNS), we explored five biological questions. First, we examined whether dysregulation of the inflammatory state within the brain-liver axis could mediate vulnerability to PNS exposure in adolescence by assessing microglial activation and pro-inflammatory cytokine expression in the dorsal and ventral hippocampus and liver, focusing on leptin's role in inflammation. We found strong microglia activation in the dorsal hippocampus of animals vulnerable to PNS exposure, along with increased transcription of pro- inflammatory markers in the liver. Moreover, an upregulation of leptin receptor expression was found in the same animals and it correlates with the inflammatory status in the liver. Second, we explored other biological mechanisms involved in PNS-induced vulnerability in adulthood, investigating disruptions in the hypothalamic-pituitary-adrenal (HPA) axis and metabolic functions and identifying candidate genes associated with psycho-metabolic comorbidities. Vulnerable males showed more pronounced metabolic issues, including weight loss, inflammation and insulin resistance, as well as upregulation of stress-related markers (FoxO1, 11β- HSD1) in the brain and liver. In contrast, resilient males demonstrated better metabolic and anti-inflammatory responses, such as increased ADIPOR1 and IL4R expression, indicating effective stress management. Additionally…
abstract: The intricate relationship between mental and physical health, particularly the co-occurrence of psychiatric disorders and metabolic conditions, has become a focus of recent research. Early-life stress (ELS) is recognized as a key factor that heightens the risk of developing mood and metabolic disorders, often resulting in comorbidities during adolescence and adulthood. This study investigates the role of ELS in contributing to psycho-metabolic comorbidities, with a focus on disruptions in the brain-liver axis, which is crucial for regulating metabolic and inflammatory processes. Using a rat model of prenatal stress (PNS), we explored five biological questions. First, we examined whether dysregulation of the inflammatory state within the brain-liver axis could mediate vulnerability to PNS exposure in adolescence by assessing microglial activation and pro-inflammatory cytokine expression in the dorsal and ventral hippocampus and liver, focusing on leptin's role in inflammation. We found strong microglia activation in the dorsal hippocampus of animals vulnerable to PNS exposure, along with increased transcription of pro- inflammatory markers in the liver. Moreover, an upregulation of leptin receptor expression was found in the same animals and it correlates with the inflammatory status in the liver. Second, we explored other biological mechanisms involved in PNS-induced vulnerability in adulthood, investigating disruptions in the hypothalamic-pituitary-adrenal (HPA) axis and metabolic functions and identifying candidate genes associated with psycho-metabolic comorbidities. Vulnerable males showed more pronounced metabolic issues, including weight loss, inflammation and insulin resistance, as well as upregulation of stress-related markers (FoxO1, 11β- HSD1) in the brain and liver. In contrast, resilient males demonstrated better metabolic and anti-inflammatory responses, such as increased ADIPOR1 and IL4R expression, indicating effective stress management. Additionally…
author: D'APRILE, ILARI
language: eng
keywords: Settore BIOS-11/A - Farmacologia
date published: 2024-12-18
date modified: 2026-07-27T20:19:10Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1125196