TRANSCRIPTOME ANALYSIS OF BRAI​​​​N REGIONS FOLLOWING TREATMENT WITH A NOVEL RELAXIN FAMILY PEPTIDE 3 RECEPTOR AGONIST IN WILDTYPE MICE

Current treatments for depression are not effective for a large number of patients, and therefore new drugs which target novel receptors in the brain are required. Relaxin family peptide 3 receptor (RXFP3) is a promising target. For example, drugs which activate RXFP3 reduce anxiety and increase motivational drive in rodents, which are key effects relevant to depression. However, these drugs do not cross the blood brain barrier (BBB) and therefore require direct injection into the brain. This project investigates a newly developed and improved RXFP3-activating drug (agonist; produced by our collaborator at the University of Queensland), that penetrates the BBB and can therefore be administered peripherally.
Male and female C57BL/6 mice were treated with a subcutaneous injection of RXFP3 agonist (1µmol/kg), or saline control. Two hours afterwards, mice were humanely killed, brains removed, and the amygdala and hippocampus extracted (these regions are relevant to depression and highly express RXFP3; n=5 per group). RNA was extracted, and RNA-Seq transcriptome sequencing performed (Australian Genome Research Facility).
In the hippocampus, RXFP3 agonist treatment increased the expression of gene sets associated with neurogenesis. In the amygdala, RXFP3 agonist treatment reduced the expression of gene sets associated with metabolism and energy expenditure, which might help explain the observed anxiolytic effects of this drug.
This project helps determine the mechanisms through which this RXFP3-activating drug alters brain. Additionally, it highlights the antidepressant potential of this class of drugs and validates this powerful research tool that can be used for future research.