Symposium
Session Room: Carron
Session Room: Carron
Sunday, June 28, 10:50 AM – 12:05 PM
Symposium 14:
Stress Across Development: From Placental Programming to Adolescent Vulnerability
Stress Across Development: From Placental Programming to Adolescent Vulnerability
The developmental origins of mental health and disease are increasingly recognized in the context of early-life stress and environmental perturbations that shape neurodevelopmental trajectories. This symposium brings together leading experts integrating human and preclinical research to examine how prenatal and adolescent stress affect brain maturation and behavioral outcomes through convergent molecular and cellular mechanisms.
Dr. Cruceanu (Sweden) will present a body of work investigating how prenatal exposures, particularly prenatal stress (PNS) and psychopharmacological agents, shape foetal neurodevelopment via the placenta-brain axis. Using longitudinal human cohorts and advanced in-vitro and ex-vivo models of perinatal tissues, her research explores how glucocorticoid receptor activation alters neuronal lineage commitment and brain architecture through transcriptional and epigenetic dysregulation – showing interesting vulnerability for GABAergic interneuron lineages (1). Furthermore, she will explore how psychopharmacological agents like classical and rapid-acting antidepressants compound or counteract the effects of stress neurobiology dysregulation via inflammatory dysregulation along the maternal-fetal interface. Employing cerebral and placental organoids as well as single-cell modalities, she will show cell-type-specific mechanisms of vulnerability and resilience. Important findings will highlight altered neuronal cell fates, activation of key transcription factors and placental coordination of stress-response pathways. The talk will emphasize critical developmental windows, sex-specific effects, and translational relevance for neurodevelopmental disorders. Dr. Riva (Italy) will address stress as a major etiological factor in mental disorders, emphasizing how PNS can induce long-lasting behavioral and neurobiological alterations extending from adolescence to adulthood. Using a validated rodent model, he will illustrate how PNS disrupts placental function, promoting inflammation and oxidative stress that interfere with normal developmental trajectories. These alterations result in reduced sociability and increased anxiety-like behavior in a subset of adolescent offspring, while others display resilience (2). The talk will highlight distinct molecular signatures along the prefrontal cortex–hippocampal axis associated with vulnerability to PNS. Finally, he will present evidence showing that a ketogenic diet during critical developmental periods can mitigate the adverse effects of gestational stress by modulating sex-dependent immune–inflammatory pathways. Dr. Gomes (Brazil) will present findings on molecular and cellular mechanisms underlying the deleterious impact of adolescent stress. The Gomes lab found that exposure to stress during adolescence in rats leads to behavioral changes and circuit deficits associated with a functional loss of parvalbumin interneurons (PVIs) and their surrounding perineuronal nets (PNNs), a specialized extracellular matrix, in the ventral hippocampus. These changes are accompanied by increased oxidative stress and enhanced activity of matrix metalloproteinase-9 (MMP-9), both contributing to the degradation of PNNs and PVI dysfunction (3). Pharmacological interventions targeting oxidative stress and MMP-9 activity, as well as a viral-mediated knockdown of MMP-9 in the ventral hippocampus, effectively prevented PVI and PNN deficits and behavioral abnormalities induced by adolescent stress. These findings point to oxidative stress and MMP-9 as key mediators of stress-induced PVI deficits and highlight potential molecular targets for early intervention in stress-related vulnerability to psychiatric disorders.
Together, these studies elucidate the complex interplay between stress biology, inflammation, oxidative stress and neuroplasticity, highlighting critical developmental windows and sex-specific vulnerability factors that may guide preventive and therapeutic strategies.
Dr. Cruceanu (Sweden) will present a body of work investigating how prenatal exposures, particularly prenatal stress (PNS) and psychopharmacological agents, shape foetal neurodevelopment via the placenta-brain axis. Using longitudinal human cohorts and advanced in-vitro and ex-vivo models of perinatal tissues, her research explores how glucocorticoid receptor activation alters neuronal lineage commitment and brain architecture through transcriptional and epigenetic dysregulation – showing interesting vulnerability for GABAergic interneuron lineages (1). Furthermore, she will explore how psychopharmacological agents like classical and rapid-acting antidepressants compound or counteract the effects of stress neurobiology dysregulation via inflammatory dysregulation along the maternal-fetal interface. Employing cerebral and placental organoids as well as single-cell modalities, she will show cell-type-specific mechanisms of vulnerability and resilience. Important findings will highlight altered neuronal cell fates, activation of key transcription factors and placental coordination of stress-response pathways. The talk will emphasize critical developmental windows, sex-specific effects, and translational relevance for neurodevelopmental disorders. Dr. Riva (Italy) will address stress as a major etiological factor in mental disorders, emphasizing how PNS can induce long-lasting behavioral and neurobiological alterations extending from adolescence to adulthood. Using a validated rodent model, he will illustrate how PNS disrupts placental function, promoting inflammation and oxidative stress that interfere with normal developmental trajectories. These alterations result in reduced sociability and increased anxiety-like behavior in a subset of adolescent offspring, while others display resilience (2). The talk will highlight distinct molecular signatures along the prefrontal cortex–hippocampal axis associated with vulnerability to PNS. Finally, he will present evidence showing that a ketogenic diet during critical developmental periods can mitigate the adverse effects of gestational stress by modulating sex-dependent immune–inflammatory pathways. Dr. Gomes (Brazil) will present findings on molecular and cellular mechanisms underlying the deleterious impact of adolescent stress. The Gomes lab found that exposure to stress during adolescence in rats leads to behavioral changes and circuit deficits associated with a functional loss of parvalbumin interneurons (PVIs) and their surrounding perineuronal nets (PNNs), a specialized extracellular matrix, in the ventral hippocampus. These changes are accompanied by increased oxidative stress and enhanced activity of matrix metalloproteinase-9 (MMP-9), both contributing to the degradation of PNNs and PVI dysfunction (3). Pharmacological interventions targeting oxidative stress and MMP-9 activity, as well as a viral-mediated knockdown of MMP-9 in the ventral hippocampus, effectively prevented PVI and PNN deficits and behavioral abnormalities induced by adolescent stress. These findings point to oxidative stress and MMP-9 as key mediators of stress-induced PVI deficits and highlight potential molecular targets for early intervention in stress-related vulnerability to psychiatric disorders.
Together, these studies elucidate the complex interplay between stress biology, inflammation, oxidative stress and neuroplasticity, highlighting critical developmental windows and sex-specific vulnerability factors that may guide preventive and therapeutic strategies.