Neurogenic and angiogenic actions of electroconvulsive seizures in adult rat brain

Sammanfattning: In the current thesis, the neurogenic and angiogenic response to electroconvulsive seizure (ECS)-treatment was investigated in the adult rat brain. ECS-treatment is an animal model for the antidepressant treatment electroconvulsive therapy (ECT), which is considered to be the most effective antidepressant treatment modality today, however with not yet fully understood modes of action. Depression, which is a common and devastating illness has recently been proposed to be caused by a decreased hippocampal neurogenesis and cellular plasticity in general, possibly due to elevated levels of the stress hormone cortisol, manifesting itself as a reduction in hippocampal volume. In the current thesis, ECS-treatment was shown to be able to oppose stress hormone-induced decrease in hippocampal neurogenesis and also induce proliferation of non-neuronal cells. A large majority of these cells were identified as being endothelial cells, and neurogenesis and angiogenesis in response to ECS-treatment seemingly occurred in concert. In addition to neurogenesis, ECS-treatment induced strong neuronal activation in the hypothalamus, co-localising with a strong angiogenic response. Endothelial cells have been shown to influence neuronal and glial function and we hypothesise that the increase in hypothalamic endothelial cell proliferation could for example influence neuroendocrine signaling. Besides possibly influencing neuronal and glial function, endothelial cells are building blocks of blood vessels. We detect a strong angiogenic response in the hippocampus, which in fact results in a 16% increase in vessel length in the molecular layer of the dentate gyrus. This finding has important implications for the trophic actions of ECS-treatment. In addition to counteracting decreases in neurogenesis, ECS-treatment increase the vascularization of a structure that has been shown to be vulnerable to stress and decrease in size in depressed patients. Understanding this angiogenic response and possibly being able to stimulate it by other means than ECS-treatment could possibly lead to the development of new and more effective antidepressant treatments.