Abstract
Background: Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms mediating these effects are poorly understood. In this talk I will focus on an important player involved in the regulation of stress response and working both downstream and upstream the activation of the Glucocorticoid Receptor (GR): the Serum Glucocorticoid kinase-1 (SGK-1).
Methods: Here I will show the long lasting impact of early life stressful events on SGK-1 signaling pathway, which may be responsible for the increased vulnerability to psychopathology. I will present gene expression and epigenetic data involved in SGK-1 modulation by using a cross species and cross tissue approach.
Results: I will start with presenting gene expression data on SGK-1 in the hippocampus of adult rats exposed or not to a prenatal stress (PNS) paradigm, where I found a significant increase in mRNA levels of SGK-1 in stressed adult animals versus controls. Importantly, we also observed an increase in SGK-1 levels in the peripheral blood of control subjects with a history of trauma as compared to those who have not experienced these traumatic events and also in a group of depressed patients as compared to controls. As SGK-1 is altered later in life although the stressor occurred early in life, we have tested the possible role of epigenetic changes as possible underlying mechanisms. In particular, I will show data on DNA methylation changes within SGK1 gene and on miRNAs targeting SGK1 both in animals and in human samples.
Conclusions: To summarize, this talk will discuss how exposures to early life stressful events can cause activation of a key-player involved in GR signaling, SGK-1, whose alterations are associated with enhanced vulnerability for stress-related psychiatric disorders, including depression.
Methods: Here I will show the long lasting impact of early life stressful events on SGK-1 signaling pathway, which may be responsible for the increased vulnerability to psychopathology. I will present gene expression and epigenetic data involved in SGK-1 modulation by using a cross species and cross tissue approach.
Results: I will start with presenting gene expression data on SGK-1 in the hippocampus of adult rats exposed or not to a prenatal stress (PNS) paradigm, where I found a significant increase in mRNA levels of SGK-1 in stressed adult animals versus controls. Importantly, we also observed an increase in SGK-1 levels in the peripheral blood of control subjects with a history of trauma as compared to those who have not experienced these traumatic events and also in a group of depressed patients as compared to controls. As SGK-1 is altered later in life although the stressor occurred early in life, we have tested the possible role of epigenetic changes as possible underlying mechanisms. In particular, I will show data on DNA methylation changes within SGK1 gene and on miRNAs targeting SGK1 both in animals and in human samples.
Conclusions: To summarize, this talk will discuss how exposures to early life stressful events can cause activation of a key-player involved in GR signaling, SGK-1, whose alterations are associated with enhanced vulnerability for stress-related psychiatric disorders, including depression.
| Original language | English |
|---|---|
| Type | Supplement |
| Publisher | Elsevier |
| Number of pages | 1 |
| Place of Publication | Psychoneuroendocrinology |
| Volume | 71 |
| DOIs | |
| Publication status | Published - Sept 2016 |