Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression

Robert J. Schloesser, Sophie Orvoen, Dennisse V. Jimenez, Nicholas F. Hardy, Kristen R. Maynard, Mahima Sukumar, Husseini K. Manji, Alain M. Gardier, Denis J. David, Keri Martinowich

Research output: Contribution to journalArticle

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. Hypothesis 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)862-867
Number of pages6
JournalBrain Stimulation
Volume8
Issue number5
DOIs
StatePublished - Sep 1 2015

Fingerprint

Neurogenesis
Antidepressive Agents
Seizures
Depression
Corticosterone
Neurons
Aptitude
Anxiety
Therapeutics
Parahippocampal Gyrus
Electroconvulsive Therapy
Wild Animals
Pharmacogenetics
Dentate Gyrus
Drinking Water
Immunohistochemistry

Keywords

  • Antidepressant
  • ECS
  • ECT
  • Hippocampus
  • Neurogenesis
  • Neuroplasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression. / Schloesser, Robert J.; Orvoen, Sophie; Jimenez, Dennisse V.; Hardy, Nicholas F.; Maynard, Kristen R.; Sukumar, Mahima; Manji, Husseini K.; Gardier, Alain M.; David, Denis J.; Martinowich, Keri.

In: Brain Stimulation, Vol. 8, No. 5, 01.09.2015, p. 862-867.

Research output: Contribution to journalArticle

Schloesser, RJ, Orvoen, S, Jimenez, DV, Hardy, NF, Maynard, KR, Sukumar, M, Manji, HK, Gardier, AM, David, DJ & Martinowich, K 2015, 'Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression', Brain Stimulation, vol. 8, no. 5, pp. 862-867. https://doi.org/10.1016/j.brs.2015.05.011
Schloesser, Robert J. ; Orvoen, Sophie ; Jimenez, Dennisse V. ; Hardy, Nicholas F. ; Maynard, Kristen R. ; Sukumar, Mahima ; Manji, Husseini K. ; Gardier, Alain M. ; David, Denis J. ; Martinowich, Keri. / Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression. In: Brain Stimulation. 2015 ; Vol. 8, No. 5. pp. 862-867.
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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. Hypothesis 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. Conclusion 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.",
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