3 years ago

Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures

Punit V Vaidya, Keri Martinowich, Mary Ann Wilson, JongAh Lee, Kathryn Baselice, Sungho Han, Lan Xiao, Jay M Baraban, Edward P Retzbach, Irving M Reti, Melissa Staley, Kellie L Tamashiro, Alec Stepanian, Andrew D Chang, Barbara L Hempstead, Paul F Worley, Sunho J Chung, Kristen Maynard, Urian Kim, Ashley Blouin
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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.

Publisher URL: https://www.nature.com/articles/npp2017252

DOI: 10.1038/npp.2017.252

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