Activating newborn neurons suppresses depression and anxiety-like behaviors

Elif Tunc-Ozcan*, Chian-Yu Peng, Yiwen Zhu, Sara R. Dunlop, Anis Contractor, John Kessler

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The etiology of major depressive disorder (MDD), the leading cause of worldwide disability, is unknown. The neurogenic hypothesis proposes that MDD is linked to impairments of adult neurogenesis in the hippocampal dentate gyrus (DG), while the effects of antidepressants are mediated by increased neurogenesis. However, alterations in neurogenesis and endophenotypes are not always causally linked, and the relationship between increased neurogenesis and altered behavior is controversial. To address causality, we used chemogenetics in transgenic mice to selectively manipulate activity of newborn DG neurons. Suppressing excitability of newborn neurons without altering neurogenesis abolish the antidepressant effects of fluoxetine. Remarkably, activating these neurons is sufficient to alleviate depression-like behavior and reverse the adverse effects of unpredictable chronic mild stress. Our results demonstrate a direct causal relationship between newborn neuronal activity and affective behavior. Thus, strategies that target not only neurogenesis but also activity of newborn neurons may lead to more effective antidepressants.

Original languageEnglish (US)
Article number3768
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

anxiety
Neurogenesis
neurons
Neurons
Anxiety
Depression
Antidepressive Agents
Dentate Gyrus
Major Depressive Disorder
disorders
etiology
disabilities
Fluoxetine
impairment
Endophenotypes
mice
Parahippocampal Gyrus
Causality
Transgenic Mice
causes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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title = "Activating newborn neurons suppresses depression and anxiety-like behaviors",
abstract = "The etiology of major depressive disorder (MDD), the leading cause of worldwide disability, is unknown. The neurogenic hypothesis proposes that MDD is linked to impairments of adult neurogenesis in the hippocampal dentate gyrus (DG), while the effects of antidepressants are mediated by increased neurogenesis. However, alterations in neurogenesis and endophenotypes are not always causally linked, and the relationship between increased neurogenesis and altered behavior is controversial. To address causality, we used chemogenetics in transgenic mice to selectively manipulate activity of newborn DG neurons. Suppressing excitability of newborn neurons without altering neurogenesis abolish the antidepressant effects of fluoxetine. Remarkably, activating these neurons is sufficient to alleviate depression-like behavior and reverse the adverse effects of unpredictable chronic mild stress. Our results demonstrate a direct causal relationship between newborn neuronal activity and affective behavior. Thus, strategies that target not only neurogenesis but also activity of newborn neurons may lead to more effective antidepressants.",
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Activating newborn neurons suppresses depression and anxiety-like behaviors. / Tunc-Ozcan, Elif; Peng, Chian-Yu; Zhu, Yiwen; Dunlop, Sara R.; Contractor, Anis; Kessler, John.

In: Nature communications, Vol. 10, No. 1, 3768, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Tunc-Ozcan, Elif

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