Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Depression is one of the leading causes of disability worldwide, yet most current treatments take several weeks to work and are ineffective for about one-third of patients. Many individuals with depression also show signs of inflammation in the body, suggesting that new therapies should consider potential inflammatory effects. The proposed research investigates the antidepressant properties of reelin, a naturally occurring protein that supports nerve cell communication and the rewiring of brain networks. Reelin is decreased in humans with depression and in rodent models of depression. We have previously shown that an optimal dose of reelin can improve depressive-like behaviors within an hour of administration in our chronic stress-based model of depression in rats and that it acts very similarly to ketamine, a rapid and effective antidepressant approved for severe and treatment-resistant depression. However, high levels of reelin may also promote inflammation, which could limit its therapeutic use. The current project will assess whether high levels of reelin produce antidepressant-like effects that are accompanied by increased inflammation in both the brain and body, and if the optimal dose of reelin reverses symptoms associated with depression without stimulating inflammation. To address the urgent need for novel fast-acting antidepressants, the present research additionally investigates the possibility of weakly stimulating the opioid system in conjunction with low-dose ketamine or reelin administration, as some evidence suggests that the opioid system is necessary for the fast antidepressant effects of ketamine. This research will help clarify the safety and potential for reelin as a fast-acting treatment for depression, and will explore sex-specific immune responses in chronic stress and with reelin administration.