Receptor G-Protein Desensitization Regulators: Involvement of Alterations in mRNA and Protein Expression in the Pathogenesis and Treatment of Major Depression

Summary : Sofia Avissar, Ph.D. plans to study the regulation of the proteins in the brain, called G protein receptors, targeted by antidepressants with the expectation that they may serve as biological markers for mood disorders and response to treatment. In the project, Dr. Avissar will study the GRK2 and ?? arrestin 1 genes and proteins activated by G protein receptor binding in animal brains and in human white blood cells obtain from controls and patients with mood disorders. Preliminary results show:elevation in ?? arrestin 1 protein and mRNA levels by various antidepressants in rat brain and reduction in ?? arrestin 1 in white blood cells of patients with depression. Lower ?? arrestin 1 was significantly correlated with severity of depressive symptoms and antidepressant treatment increased levels. These findings, Dr. Avissar says, support a role of post receptor regulatory proteins in mood disorder pathophysiology and suggest their involvement in the biochemical mechanism for antidepressant induced G protein receptor down regulation. The proposed study aims to identify new beyond receptor biochemical sites, possibly leading to optimization of antidepressant treatment and new drug targets against mood disorders.