Sarah Sun
Summer Research Description: Adenosine-to-inosine mRNA editing of gene transcripts has been implicated in major psychiatric disorders, and alterations in 5HT2C editing have been observed in suicide victims with a history of major depression and in response to antidepressant treatment. Editing of gene transcripts encoding the 2C-subtype of serotonin receptor (5HT2C) can produce up to 24 receptor isoforms that differ in their G-protein coupling efficacy and constitutive activity. Here we propose that mice exhibiting chronic stress-induced depressive phenotypes exhibit significantly different 5HT2C editing distributions from control mice. We will apply random stressors to a subset of C57BL/6J mice once daily over a period of seven weeks and administer novelty induced hypophagia and forced-swim behavioral paradigms to identify the animals exhibiting a depression-like phenotype. A deep-sequencing approach will be used to compare editing levels for 5HT2C transcripts in six brain regions of depressed and healthy mice. Differences in editing profiles between animals with depression-like symptoms and control mice would suggest not only a critical role for 5HT2C editing in the etiology of depression but also the possibility of targeting editing mechanisms in the treatment of depression.