Anagh Sinha L&S Sciences
Understanding the effect of Cnr2 knockout on microglial immune response
Major Depressive Disorder (MDD) is a devastating neuropsychiatric disorder affecting 16 million people in the United States, with an estimated public burden of $210 billion/year. Yet, mechanisms leading to MDD progression remain poorly understood. Persistent activation of microglia, resident immune cells of the brain, has been previously linked to depression. This activation also appears to be linked with changes in expression of cannabinoid receptor 2 (CB2). Targeted activation of CB2 has shown to bias microglia to a pro resolution state, but whether proper CB2 expression is necessary for the normal immune response is unknown. I plan to test if CB2 expression is linked to the natural immune response using a CRISPR deletion of the Cnr2 gene to create a CB2 knockout (Cnr2KO) cell line. Then, I intend to compare the natural immune response to that of the Cnr2KO line. This project will suggest to what degree the microglial immune response needs normal CB2 expression. We can then determine the efficacy of drugs targeting CB2 that alter microglial activity in relation to MDD.