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Adult hippocampal neurogenesis in depression

Abstract

The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. Here we evaluate adult hippocampal neurogenesis as a candidate mechanism for the etiology of depression and as a substrate for antidepressant action. Current evidence indicates that adult hippocampal neurogenesis may not be a major contributor to the development of depression, but may be required for some of the behavioral effects of antidepressants. We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants.

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Figure 1: Antidepressants exert their behavioral effects through neurogenesis-dependent and neurogenesis-independent pathways.
Figure 2: Distinct roles for dorsal and ventral hippocampal neurogenesis in regulation of emotion.

Jessica Iannuzzi

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Acknowledgements

The authors are grateful to H. Scharfman, J. Gordon, C. Lacefield, M. Drew and E.D. Leonardo for their critical comments on earlier versions of this manuscript. This work was supported by NARSAD (A.S. and R.H.) and the US National Institute of Mental Health (R.H.).

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Correspondence to Amar Sahay or Rene Hen.

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R.H. is a founder of Braincells, a company that explores the therapeutic potential of hippocampal neurogenesis.

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Sahay, A., Hen, R. Adult hippocampal neurogenesis in depression. Nat Neurosci 10, 1110–1115 (2007). https://doi.org/10.1038/nn1969

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