Chronic restraint stress induces hippocampal memory deficits by impairing insulin signaling

Hanwoong Woo, Caroline Jeeyeon Hong, Seonghee Jung, Seongwon Choe, Seong-Woon Yu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)
35 Downloads (Pure)


Chronic stress is a psychologically significant factor that impairs learning and memory in the hippocampus. Insulin signaling is important for the development and cognitive function of the hippocampus. However, the relation between chronic stress and insulin signaling at the molecular level is poorly understood. Here, we show that chronic stress impairs insulin signaling in vitro and in vivo, and thereby induces deficits in hippocampal spatial working memory and neurobehavior. Corticosterone treatment of mouse hippocampal neurons in vitro caused neurotoxicity with an increase in the markers of autophagy but not apoptosis. Corticosterone treatment impaired insulin signaling from early time points. As an in vivo model of stress, mice were subjected to chronic restraint
stress. The chronic restraint stress group showed downregulated insulin signaling and suffered deficits in spatial working memory and nesting behavior. Intranasal insulin delivery restored insulin signaling and rescued hippocampal deficits. Our data suggest that psychological stress impairs insulin signaling and results in hippocampal deficits, and these effects can be prevented by intranasal insulin delivery.
Original languageEnglish
Article number37
Pages (from-to)1-13
Number of pages13
JournalMolecular Brain
Issue number37
Publication statusPublished - 3 Jul 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Chronic restraint stress
  • corticosterone
  • insulin signaling
  • intranasal insulin delivery
  • nesting
  • Y-maze


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