Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment.
Major depression is often associated with elevated glucocorticoid levels. High levels of glucocorticoids reduce neurogenesis in the adult rat hippocampus. Electroconvulsive seizures (ECS) can enhance neurogenesis, and we investigated the effects of ECS in rats where glucocorticoid levels were elevated in order to mimic conditions seen in depression. Rats given injections of corticosterone or vehicle for 21 days were at the end of this period treated with either a single or five daily ECSs. Proliferating cells were labelled with bromodeoxyuridine (BrdU). After 3 weeks, BrdU-positive cells in the dentate gyrus were quantified and analyzed for co-labelling with the neuronal marker neuron-specific nuclear protein (NeuN). In corticosterone-treated rats, neurogenesis was decreased by 75%. This was counteracted by a single ECS. Multiple ECS further increased neurogenesis and no significant differences in BrdU/NeuN positive cells were detected between corticosterone- and vehicle-treated rats given five ECS. Approximately 80% of the cells within the granule cell layer and 10% of the hilar cells were double-labelled with BrdU and NeuN. We therefore conclude that electroconvulsive seizures can increase hippocampal neurogenesis even in the presence of elevated levels of glucocorticoids. This further supports the hypothesis that induction of neurogenesis is an important event in the action of antidepressant treatment.
Hellsten
Johan
J
Molecular Psychiatry Unit, Wallenberg Neuroscience Center, Lund, Sweden.
Wennström
Malin
M
Mohapel
Paul
P
Ekdahl
Christine T
CT
Bengzon
Johan
J
Tingström
Anders
A
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D003866:Depressive Disorder / Q000503:physiopathology* / Q000628:therapy*; D004334:Drug Administration Schedule; D004565:Electroconvulsive Therapy; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D009687:Nuclear Proteins; D003345:Corticosterone