Publications by authors named "P J Schoonheim"

In humans, two splice variants of the glucocorticoid receptor (GR) exist: the canonical α-isoform, and the β-isoform, which has been shown to have a dominant-negative effect on hGRα. Previously, we have established the occurrence of a GR β-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GRβ (zGRβ). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGRβ but no such effect was observed in zebrafish PAC2 cells using induction of the fk506 binding protein 5 (fkbp5) gene as readout.

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Article Synopsis
  • Glucocorticoids help restore balance in the body after stress by providing negative feedback to the brain's stress circuits, and their dysfunction may increase stress-related issues like depression and anxiety.
  • Researchers studied mutant zebrafish lacking functional glucocorticoid receptors, finding these fish showed heightened stress responses and abnormal cortisol levels even at a young age.
  • Treatment with Fluoxetine (Prozac) helped reduce stress responses in mutant zebrafish, indicating that the relationship between glucocorticoid and serotonin signaling is similar across species, paving the way for further research on stress disorders.
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Upon binding of cortisol, the glucocorticoid receptor (GR) regulates the transcription of specific target genes, including those that encode the stress hormones corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone. Dysregulation of the stress axis is a hallmark of major depression in human patients. However, it is still unclear how glucocorticoid signaling is linked to affective disorders.

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Glucocorticoids regulate a wide range of systems in vertebrate organisms, and their effects are mediated by the glucocorticoid receptor (GR). The responsiveness to glucocorticoids differs largely between individuals. Resistance to glucocorticoids is an important medical problem, since it limits the efficacy of glucocorticoids when they are used to treat immune-related diseases like asthma and rheumatoid arthritis.

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The optokinetic response (OKR) to a visual stimulus moving at constant velocity consists of a series of two alternating components, a slow phase, during which the eyes follow the stimulus, and a quick phase, which resets the eyes to begin a new response cycle. The quick phases of the OKR resemble the saccades observed during free viewing. It is unclear to what extent the premotor circuitry underlying these two types of jerky, conjugate eye movements is conserved among vertebrates.

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