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Ageing abolishes the effects of fluoxetine on neurogenesis

Molecular Psychiatry volume 14, pages 856–864 (2009)Cite this article

Abstract

Depression constitutes a widespread condition observed in elderly patients. Recently, it was found that several drugs employed in therapies against depression stimulate hippocampal neurogenesis in young rodents and nonhuman primates. As the rate of neurogenesis is dramatically reduced during ageing, we examined the influences of ageing on neurogenic actions of antidepressants. We tested the impact of fluoxetine, a broadly used antidepressant, on hippocampal neurogenesis in mice of three different age groups (100, 200 and over 400 days of age). Proliferation and survival rate of newly generated cells, as well as the percentage of cells that acquired a neuronal phenotype were analyzed in the hippocampus of mice that received fluoxetine daily in a chronic manner. Surprisingly, the action of fluoxetine on neurogenesis was decreasing as a function of age and was only significant in young animals. Hence, fluoxetine increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age). The data indicate that the action of fluoxetine on neurogenesis is highly dependent on the age of the treated individual. Although the function of neurogenesis in the clinical manifestation of depression is currently a matter of speculation, this study clearly shows that the therapeutic effects of antidepressants in elderly patients are not mediated by neurogenesis modulation.

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Acknowledgements

This study was supported by the Bavarian State Ministry of Sciences, Research and Arts (ForNeuroCell grant), the German Federal Ministry of Education and Research BMBF grants 01GN0507 and 01GG0706.

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Authors and Affiliations

  1. Department of Neurology, University of Regensburg, Regensburg, Germany

    S Couillard-Despres, C Wuertinger, M Kandasamy, M Caioni, K Stadler, R Aigner, U Bogdahn & L Aigner

  2. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria

    L Aigner

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  1. S Couillard-Despres
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  2. C Wuertinger
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Correspondence to S Couillard-Despres.

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Couillard-Despres, S., Wuertinger, C., Kandasamy, M. et al. Ageing abolishes the effects of fluoxetine on neurogenesis. Mol Psychiatry 14, 856–864 (2009). https://doi.org/10.1038/mp.2008.147

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