Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Hyeon Son, Mounira Banasr, Miyeon Choi, Seung Yeon Chae, Pawel Licznerski, Boyoung Lee, Bhavya Voleti, Nanxin Li, Ashley Lepack, Neil M. Fournier, Ka Rim Lee, In Young Lee, Juhyun Kim, Joung Hun Kim, Yong Ho Kim, Sung Jun Jung, Ronald S. Duman

Research output: Contribution to journalArticle

Abstract

Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.

Original languageEnglish (US)
Pages (from-to)11378-11383
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number28
DOIs
StatePublished - Jul 10 2012
Externally publishedYes

Keywords

  • Anhedonia
  • BDNF
  • Despair
  • Synaptogenesis

ASJC Scopus subject areas

  • General

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  • Cite this

    Son, H., Banasr, M., Choi, M., Chae, S. Y., Licznerski, P., Lee, B., Voleti, B., Li, N., Lepack, A., Fournier, N. M., Lee, K. R., Lee, I. Y., Kim, J., Kim, J. H., Kim, Y. H., Jung, S. J., & Duman, R. S. (2012). Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress. Proceedings of the National Academy of Sciences of the United States of America, 109(28), 11378-11383. https://doi.org/10.1073/pnas.1201191109