One of the core approaches my lab uses to model depressive-like symptoms in mouse models is the social defeat paradigm. This paradigm allows my lab to simulate behavioral conditions that lead to the onset of depressive-like symptoms which we can then use to study and/or treat. My lab uses this method because it allows us to study the onset of depressive-like symptoms in as close to a real world setting as possible, while not relying on the monoamine hypothesis that states that depression is largely caused by a lack of serotonin or norepinephrine in the brain. As the focus of my summer research work, I have been assisting various lab members on different projects that use the paradigm to study the effectiveness of different treatment methods for depression.
Currently, I am helping a fellow undergraduate student study the relationship between behavior and microbiology in the lateral habenula on the brain. Scientists have found that over excitability in the lateral habenula is correlated with depressive-like symptoms while a smaller region in the lateral habenula has been shown to inhibit these symptoms. Previous data has suggested that a protein, MeCP2, has an antidepressant like effect when phosphorylated in the small region of the lateral habenula. The project that I am assisting with seeks to understand whether MeCP2 is phosphorylated in the brains of mice that have been treated with an anti-depressant called imipramine.
The experimental set up involves 10 days of social defeat followed by 28 days of imipramine injections, or 27 days of saline injections and 1 day of imipramine injections. We will then test 6 mice out of each experimental group and 6 mice of the control group that receives 28 saline injections to isolate and measure MeCP2 levels in the lateral habenula. Our hypothesis is that the mice that have had 28 days of imipramine injections will have the strongest anti-depressant effects and will have the highest levels of MeCP2.
