Grant: CIHR Fellowship

Depression is a debilitating mental illness, affecting over 264 million people worldwide and ~3.2 million people in Canada. The modest efficacy of current antidepressant therapies compels a better understanding of the mechanisms involved in the development of depression. Since stress is a precipitating factor for depression, chronic stress exposure is used in research to mimic aspects of this illness in rodents. In the present study, we will first focus on identifying gene expression changes in brain cells called astrocytes when subjects are exposed to chronic stress (rodents) or suffered from depression (post mortem human brains). Common changes in both species will lead to the identification of highly evolutionarily conserved cellular mechanisms and astrocytic genes involved in depression and stress-related illnesses. Importantly, it is already known that one astrocytic gene (glutamate transporter-1 or GLT-1) is reduced in both human depression and chronic stress rodent models. Thus, we will then determine if GLT1 gene deletion specifically in astrocytes can directly cause emotion-related behaviours and synapse loss in rodents, deficits similar to human depression. Further we will measure astrocyte activity in the free moving animals using a technique called fiber photometry, which consists of implanting a fiber optic cannula in a brain region of interest while monitoring behaviour. This technique will allow us to investigate the astrocyte activity changes over the course of chronic stress exposure, or following GLT1 gene deletion. Together, this work will provide critical insight into the astrocyte-specific mechanisms underlying depression and chronic stress and will establish a link between changes in astrocyte activity, emotion-behaviour and neuronal plasticity.