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Posted on Mar 22, 2018, 4 p.m.
Scientists at The Scripps Research Institute have discovered a possible new target for treating major depressive disorder, which can be a debilitating disease affecting more than an estimated 16 million adults within the USA alone, as published in the journal eLife.
Individuals with high levels of enigmatic orphan receptor GPR158 have been shown to be more susceptible to depression following chronic stress. There is a need to develop new drug targets in major depressive disorder. It is hoped that this research is a step in that direction. Pharmacological treatments currently used can take up to a month to start working and they are not always effective.
GPR158 was targeted by researchers after discovering the protein is elevated in individuals with major depressive disorder. To develop a better understanding of GPR158’s role in depression researchers studied mice of both sexes with and without GPR158 receptors. Behavioral testing on mice with elevated levels showed signs of depression following chronic stress. Suppression of GPR158 was observed to protect the mice from developing depression symptom behaviors and made them resilient to stress, as the mice did not alter behaviour after chronic stress.
Researchers were able to demonstrate that GPR158 affects important signalling pathways that are involved in mood regulation in the prefrontal cortex, but the exact mechanisms have yet to be established. GPR158 appears to work downstream from other brain systems such as GABA, but this is new biology with a lot of work needing to be done to learn more. Genome analysis using new tools to identify orphan receptors such as GPR158 are making advances in finding possible targets that are the untapped biology of our genomes uncovering potential for significant development of innovative new therapeutics.
Materials provided by Scripps Research Institute.
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Journal Reference:
Laurie P Sutton, Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J Renner, Samuel M Young, Baoji Xu, Hyungbae Kwon, Kirill A Martemyanov. Orphan receptor GPR158 controls stress-induced depression. eLife, 2018; 7 DOI: 10.7554/eLife.33273
