90% of antidepressant drugs are based on the monoamine hypothesis, thought to explain how depression arises based on depressed individuals lacking the monoamine neurotransmitters serotonin and norepinephrine, and are designed to recalibrate the two amines, but according to the researchers 30% of the drugs aren’t effective.
RGS8 protein has been shown in previous studies to regulate hormone receptor MCHR1 they team designed this study to explore even further. RGS8 appears to be expressed in brain regions involved in movement and mood regulation, when active MCHR1 helps to regulate mood, sleep, and food. MCHR1 was found to be inactivated in cultured cells by RGS8 bringing forth the hypothesis that less RGS8 causes increase in depressive behavior, which had not been investigated in living animals previously. Model mice of depression were developed to build off previous work and investigate this hypothesis.
Swim tests to measure how long each animal is active before subtracting that time from the to test time to provide immobility times, the team found animals expressing more RGS8 in their nervous system had shorter immobility times than those with normal amounts. RGS8 animals had even shorter immobility times when given antidepressants that act on monoamines, when given an agent that stops MCHR1 from functioning immobility stayed the same. Examination of the animal brains under microscope to investigate relationship between MCHR1 and RGS8, specifically looking at the size of cilia extending from cells in hippocampus area CA1 which has the highest level of RGS8, the team found that not only did the RGS8 mice show less depressive behavior but they also had longer cilia, meaning animals given agents that stopped function of MCHR1 had longer cilia.
Researchers have observed over the last decade that dysfunctional cilia are linked to obesity, kidney disease, and retina disease. Their association with mood disorders is not fully understood, but the team thinks RGS8 is a good candidate showing promise for the development of new antidepressants, which will be focus for further studies in the future.
