Identification of key regulators that mediate antidepressant effects using cell type-specific transcriptional profiling in the mouse hippocampus

Abstract

Major depressive disorder (MDD) is a highly prevalent mental disorder and a leading cause of disability and suicidal commitment worldwide. Despite wide clinical use for the depressive patients, the current antidepressant medications, including the selective serotonin reuptake inhibitors (SSRIs) and the serotonin/norepinephrine reuptake inhibitors (SNRIs), have been limited to relieve major depression efficiently on time, but without any unnecessary side effects. Seriously, the SSRIs/SNRIs generally take several weeks to display significant therapeutic benefits, in spite of their immediate effect on serotonergic neurotransmission. This therapeutic delay have suggested importance of slow adaptive changes in neural circuits over prolonged period of drug treatment, possibly via gene regulation and protein translation. However, the innate complexity of the neural circuits especially with the heterogeneity of the neural cell types hampers our challenge to decipher the precise molecular mechanism of the drug actions in the brain. In this talk, I am going to briefly introduce my research project that aims to explore the cell type-specific transcriptional mechanisms underlying the drug-induced neuro-adaptive changes in the hippocampus. The current study may contribute to our understanding the therapeutic mechanisms of the current antidepressant medication and hopefully further to the development of more effective and rapid-acting antidepressants with less side effects.