To better understand GPR158’s role, the scientists studied male and female mice with and without GPR158 receptors.
Behavioural tests revealed that both male and female mice with elevated GPR158 show signs of depression following chronic stress. On the flip side, suppression of GPR158 protects mice from developing depressive-like behaviours and make them resilient to stress.
For the study, published in the journal eLife, the researchers also examined why GPR158 has these effects on depression.
The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasised that the exact mechanisms remain to be established.
The researchers explained that GPR158 is a so-called “orphan receptor” — which gets its name because its binding partner/partners are unknown — with a poorly understood biology and mechanism of action.
GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain’s inhibitory control and adrenergic system involved in stress effects.