Studies on cellular changes and amnesia in a rat model of electroconvulsive therapy

Sammanfattning: Electroconvulsive therapy (ECT) is a well-established treatment for severe depressive disorder, but its clinical use has been limited by concerns about side effects such as memory disturbances. Despite over 70 years in clinical use, the exact mechanisms of action behind the therapeutic or adverse effects are not fully understood. Enhanced brain plasticity, including neurogenesis, angiogenesis and synaptic reorganization, has been suggested to underlie the therapeutic effects of ECT. In the current thesis, we have studied cellular changes in an animal model of ECT - electroconvulsive seizures (ECS) - in limbic brain regions implicated in the pathophysiology of depression. In the first paper, we show that ECS enhances neuronal activation and endothelial cell proliferation in specific regions of the hypothalamus. In paper II and III we demonstrate a low-grade glial cell activation in all limbic regions investigated except the hypothalamus, and an increased recruitment of peripheral macrophages to the hippocampus. Endothelial cell proliferation and glial cell activation might reflect the enhanced brain plasticity following ECS, but could also be part of an inflammatory response. Inflammation is induced following brain insults, and the cognitive deficits after ECT have raised some concerns about ECT causing brain damage. Although most studies have shown no cell damage following ECT or ECS, limited cell loss might occur under certain circumstances. In the final paper we tried to block the glial cell activation in order to investigate whether this affected memory function. We also measured apoptotic cell death and found that ECS gave rise to a slightly increased cell loss in hippocampal subregions. Lithium treatment abolished the ECS-induced retrograde amnesia, but the level of glial cell activation and cell death were unchanged or even slightly increased. Our results suggest that the ECS-induced amnesia is uncoupled from cell loss and glial cell activation, and that lithium treatment might be a potential agent for attenuation of ECS-induced retrograde amnesia.