Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic–pituitary–adrenal axis activity.
To better understand how PhD graduates have prepared for the nonacademic job market, we surveyed life science PhD and postdoctoral graduates from the University of Toronto who were employed in non-academic sectors. We also surveyed life science PhD and postdoctoral trainees to assess their engagement in career preparation activities. PhD professionals employed in non-academic sectors had engaged in various career preparation activities during their training. Some activities had a higher perceived impact on the path to employment than others. Trainees had also engaged in such activities, but those rated by professionals as having a highly positive impact on their path to employment were engaged in by only a minority of trainees. The proportion of trainees who wished to work in a non-academic sector was higher among those who were closer to program completion. Like professionals, many trainees reported facing barriers to pursuing career development activities. Our findings suggest that PhD trainees seeking to work in nonacademic sectors should engage in career preparation activities, particularly those that involve experiential learning. By supporting co-curricular programming and reducing barriers to participation in career development activities, academic administrators and faculty have the opportunity to support trainees' professional development beyond the laboratory.
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