The contribution of CNS inflammation and Glycogen Synthase Kinase-3 (GSK-3)-cascades on adverse memory learning on mouse models of emotional stress

This thesis aimed to study the role of the glycogen-synthase kinase 3 (GSK-3) expression, inflammatory mechanisms and associated changes in the brain of mice. For that purpose, two new mouse paradigms of depression were used, the ultrasound stress model of “emotional stress” and the model of enhanced contextual learning of adverse memories of modified swim test. The results obtained in these studies suggest overlapping molecular mechanisms of over-expression of two isoforms of GSK-3 and proinflammatory mechanisms along with oxidative stress to underlie distinct aspects of depressive syndrome. In addition, identified was GSK-3α as one of the potential targets of depression treatment and demonstrated was that thiamine (vitamin B1) drugs can have a potential in reducing depressive-like changes associated with stress.