title: Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats.
abstract: Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently documented an initial 2.6-fold increase in neurogenesis following a clinical relevant schedule of ECS, a treatment also rescuing depression-like behavior in rats. However, these results gave no demonstration of the longevity of newly generated neurons. The present study is a direct continuation of the previous work aiming to test the hypothesis that rats subjected to ECS in combination with chronic restraint stress (CRS) display increased formation of new hippocampal neurons, which have a potential for long-term survival. Furthermore, using mediation analysis, we tested if an ECS-induced increase in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new BrdU-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found that, while ECS increases neurogenesis, this formation of new neurons was not associated to ameliorated immobility in the FST. This implies that other ECS-induced effects than neurogenesis must be part of mediating the antidepressant action of ECS. Taken together, the results of the present study contribute to the basic understanding of the neurogenic effects of ECT, and demonstrate that ECS, neurogenesis and anti-depressant behavior are not directly linked. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurology, Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: Mikkel Vestergaard
authors.initials: MV
authors.lastname: Olesen
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen and Mental Health Center Copenhagen, Copenhagen, Denmark.|Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.affiliation: Department of Neurology, Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Folke
authors.affiliation: Department of Neurology, Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.|Department of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy; D005500:Follow-Up Studies; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011897:Random Allocation; D017208:Rats, Wistar; D012149:Restraint, Physical; D013997:Time Factors
chemical_list: D001973:Bromodeoxyuridine
keywords: electroconvulsive stimulation; long-term survival; neurogenesis; stereology