A Glial Role in the Action of Electroconvulsive Therapy

Abstract: The aim of the current thesis was to investigate glial responses to electroconvulsive seizures (ECS), an animal model of the fast-acting antidepressant treatment electroconvulsive therapy (ECT). Depression, a common and devastating disorder, has in recent years been associated with volumetric changes in prefrontal cortex, hippocampus and amygdala, brain regions known to be implicated in emotional behavior. Post-mortem analysis of brain tissue from depressed patients, have suggested that neuronal and glial pathology, seen both as changes in cellular densities and glial cell loss, may underlie the depression-associated volumetric changes. The observations that depressed patients often display high levels of the stress hormone cortisol, and that elevated levels of cortisol have been linked with both hippocampal volume reductions and depression, have lead to the assumption that cortisol may underlie the volumetric changes seen in depressed patients. Support for this idea is found in preclinical studies showing that corticosterone (the rat homologue to cortisol) induce both depression-like behavior and hippocampal volume reductions. Studies have also shown that high levels of corticosterone suppress the formation of new neurons and glial cells in rat hippocampus. The studies of this thesis demonstrate that the antidepressant treatment modality ECS upregulates glial proliferation and, moreover, opposes the inhibitory effect of corticosterone on glial cell renewal. We also demonstrate that ECS, without inducing reactive gliosis (a hallmark of brain damage), increase glial cell activity. Given that glial cells (by supporting, communicating with and nourishing the surrounding neurons) play a vital role in neuronal network, we hypotehesize that these glial cell responses may, at least in part, be involved in the antidepressant action of ECT.