Researchers in the Netherlands used zebrafish to understand how the receptors responsible for stress work in the brain.

Stress responses are mediated by the hormone cortisol, which acts in the brain through two types of proteins – mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). These receptors can form sets of two proteins – dimers – either from the same type of protein (homodimers) or from the two types of protein (heterodimers), with the latter’s role in the brain’s stress response still unknown. 

Researchers at Leiden University used zebrafish to study the role of heterodimers because their brain and behaviour can be easily monitored and they can be genetically modified. They created zebrafish with genetically modified versions of the proteins that would force them to form either homo- or heterodimers.  

The researchers discovered that only zebrafish with heterodimers were hyperactive – a normal response to cortisol – and had alterations in the expression of genes in the brain, showing that they are indispensable in activating stress response. 

Marcel Schaaf, leader of the study published in Molecular Psychiatry and researcher at Leiden University, explained: “Our findings might explain certain stress-induced behavioral effects (e.g., anxiety-like behavior), and may therefore be helpful in development of therapies against stress-related mental disorders.”