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Hippocampal neurogenesis and depression.

Amar Sahay1, René Hen

  • 1Department of Neuroscience, Columbia University, New York, NY 10032, USA.

Novartis Foundation Symposium
|May 24, 2008
PubMed
Summary

Antidepressant effects depend on new neuron growth in the hippocampus. Disrupting this process, called hippocampal neurogenesis, blocks antidepressant responses and synaptic plasticity, showing its crucial role.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Chronic antidepressant treatments are known to increase adult hippocampal neurogenesis.
  • The functional significance of this increased neurogenesis for antidepressant efficacy remains largely unknown.

Purpose of the Study:

  • To investigate the functional importance of adult hippocampal neurogenesis for the behavioral effects of antidepressants.
  • To determine if blocking neurogenesis affects antidepressant-induced behavioral responses.

Main Methods:

  • Utilized X-irradiation to disrupt neurogenesis in a specific region of the mouse hippocampus.
  • Employed a genetic strategy to ablate adult neural progenitor cells.
  • Assessed behavioral responses to antidepressants in conjunction with neurogenesis disruption.

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  • Investigated long-term potentiation in the dentate gyrus.

    • Main Results:

    • Disrupting hippocampal neurogenesis via X-irradiation prevented the neurogenic and behavioral effects of two antidepressant classes.
    • Ablating adult progenitor cells genetically also resulted in a lack of antidepressant effect.
    • Identified antidepressant-stimulated long-term potentiation in the dentate gyrus, dependent on young neurons.

    Conclusions:

    • Adult hippocampal neurogenesis is essential for the behavioral effects of chronic antidepressant treatments.
    • Increased synaptic plasticity in the dentate gyrus, mediated by new neurons, is a key mechanism for antidepressant action.