title: Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression.
abstract: BACKGROUND
  Neurogenesis continues throughout life in the hippocampal dentate gyrus. Chronic treatment with monoaminergic antidepressant drugs stimulates hippocampal neurogenesis, and new neurons are required for some antidepressant-like behaviors. Electroconvulsive seizures (ECS), a laboratory model of electroconvulsive therapy (ECT), robustly stimulate hippocampal neurogenesis.
  
  
  OBJECTIVE
  ECS requires newborn neurons to improve behavioral deficits in a mouse neuroendocrine model of depression.
  
  
  METHODS
  We utilized immunohistochemistry for doublecortin (DCX), a marker of migrating neuroblasts, to assess the impact of Sham or ECS treatments (1 treatment per day, 7 treatments over 15 days) on hippocampal neurogenesis in animals receiving 6 weeks of either vehicle or chronic corticosterone (CORT) treatment in the drinking water. We conducted tests of anxiety- and depressive-like behavior to investigate the ability of ECS to reverse CORT-induced behavioral deficits. We also determined whether adult neurons are required for the effects of ECS. For these studies we utilized a pharmacogenetic model (hGFAPtk) to conditionally ablate adult born neurons. We then evaluated behavioral indices of depression after Sham or ECS treatments in CORT-treated wild-type animals and CORT-treated animals lacking neurogenesis.
  
  
  RESULTS
  ECS is able to rescue CORT-induced behavioral deficits in indices of anxiety- and depressive-like behavior. ECS increases both the number and dendritic complexity of adult-born migrating neuroblasts. The ability of ECS to promote antidepressant-like behavior is blocked in mice lacking adult neurogenesis.
  
  
  CONCLUSIONS
  ECS ameliorates a number of anxiety- and depressive-like behaviors caused by chronic exposure to CORT. ECS requires intact hippocampal neurogenesis for its efficacy in these behavioral indices.
authors.affiliation: University of Maryland School of Medicine, Department of Psychiatry, Baltimore, MD, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schloesser
authors.affiliation: Université Paris Sud, INSERM UMR S 1178, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Orvoen
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
authors.forename: Dennisse V
authors.initials: DV
authors.lastname: Jimenez
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Hardy
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Maynard
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
authors.forename: Mahima
authors.initials: M
authors.lastname: Sukumar
authors.affiliation: Global Therapeutic Area Head, Neuroscience, Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.affiliation: Université Paris Sud, INSERM UMR S 1178, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.affiliation: Université Paris Sud, INSERM UMR S 1178, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA; Departments of Psychiatry and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: keri.martinowich@libd.org.
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D000089662:Doublecortin Protein; D004565:Electroconvulsive Therapy; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein
keywords: Antidepressant; ECS; ECT; Hippocampus; Neurogenesis; Neuroplasticity