Original Article

Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures

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Published online:

Abstract

Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer that Narp knockout mice undergo normal seizure activity in this paradigm, yet fail to display antidepressant-like behavioral effects of ECS. Although Narp deletion does not suppress ECS-induced proliferation in the dentate gyrus, it blocks dendritic outgrowth of immature granule cell neurons in the dentate molecular layer induced by ECS. Taken together, these findings indicate that Narp contributes to the antidepressant action of ECT and implicate the ability of ECS to induce dendritic arborization of differentiating granule cells as a relevant step in eliciting this response.

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Acknowledgements

We sincerely thank Eric and Alison Jager for their very generous support of this project.

Author information

Affiliations

  1. The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA

    • Andrew D Chang
    • , Punit V Vaidya
    • , Edward P Retzbach
    • , Sunho J Chung
    • , Urian Kim
    • , Kathryn Baselice
    • , Alec Stepanian
    • , Melissa Staley
    • , Lan Xiao
    • , Ashley Blouin
    • , Sungho Han
    • , JongAh Lee
    • , Paul F Worley
    • , Kellie L Tamashiro
    • , Keri Martinowich
    • , Mary Ann Wilson
    • , Jay M Baraban
    •  & Irving M Reti
  2. Lieber Institute for Brain Development, Baltimore, MD, USA

    • Kristen Maynard
    •  & Keri Martinowich
  3. Weill Cornell Medical College, Department of Medicine, New York, NY, USA

    • Barbara L Hempstead
  4. The Kennedy Krieger Institute, Baltimore, MD, USA

    • Mary Ann Wilson

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Correspondence to Irving M Reti.

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