Topic: glucocorticoid receptor

Stress induces aversive memory overgeneralization, a hallmark of many psychiatric disorders. Memories for events are encoded by a sparse ensemble of principal neurons active during an event, termed an engram ensemble. Using engram labeling tools, molecular sensors, optogenetics and CRISPR-Cas9 gene editing in specific neuronal populations we examined the molecular and circuit processes mediating stress-induced threat memory overgeneralization in mice. We found that stress, acting via corticosterone, increases the density of engram ensembles supporting a threat memory and this less sparse engra

The brain undergoes important growth and plasticity during prenatal development. Altered activation of the glucocorticoid receptor (GR) system is one of the factors mediating stress effects during this time, likely through transcriptional dysregulation. To investigate these processes in a human-specific in vitro system, we used induced pluripotent stem cell-derived 3-dimensional brain organoids. To determine cell-type specific GR activation response, we profiled the transcriptomes of thousands of individual cells using single-cell transcriptomic analyses following glucocorticoids exposure acut

Stress-related psychiatric disorders have been associated with polymorphisms in the gene encoding FK506-binding protein 5(FKBP5), a co-chaperone of the glucocorticoid receptor(GR). Stress response is coordinated by the hypothalamic-pituitary-adrenal(HPA) axis, through secretion of glucocorticoids(GC). Additionally, the HPA is a site of convergence of the circadian clock and the stress response systems. Physiologically, GCs act as molecular effectors of circadian rhythm that synchronize transcriptional and metabolic activity in peripheral tissues. However, not much is understood about the analo

The synergistic effects on neuronal plasticity of acute glucocorticoids levels increase and the BDNF-TRKB signaling indicate a deep interconnection between the two pathways. Moreover, chronic stress with elevated glucocorticoids levels and downregulation of TRKB signaling associated with reduced BDNF are both involved in the pathophysiology of different psychiatric disorders.In this study we investigated in vitro the molecular mechanisms underlying the interplay of glucocorticoids and TRKB signaling. We found that the glucocorticoid receptor physically interacts with TRKB, modulating its dimer

Post-traumatic stress disorder (PTSD) is a debilitating stress-related psychiatric disorder that can develop following trauma exposure in some individuals. Among others, it is characterized by a dysregulated hypothalamic – pituitary – adrenal axis, which is predominantly regulated by the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The neurobiological processes leading to disease remain largely unknown. In vitro models are promising tools to investigate specific neurobiological underpinnings of the stress response in the brain. Here, we investigated the suitability of

Prenatal pathologies like fetal hypoxia or prenatal stress are increasingly recognized contributors to later-life neuropsychiatric diseases. These pathologies often co-occur, making it challenging to distinguish their individual effects. To address this, we modeled prenatal severe hypoxia (PSH) associated with maternal stress, or prenatal intrauterine ischemia (PII). Both adult PSH and PII rats showed elevated HIF1α levels in the hippocampus (HPC), but only PSH rats exhibited an impaired circadian glucocorticoid rhythm, demonstrating the suitability of both models for the research objectives.C