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Research Database PMU-SQQUID

Ageing abolishes the effects of fluoxetine on neurogenesis.
Couillard-Despres, S; Wuertinger, C; Kandasamy, M; Caioni, M; Stadler, K; Aigner, R; Bogdahn, U; Aigner, L;
MOL PSYCHIATR. 2009; 14(9): 85-64.
Originalarbeiten (Zeitschrift)

PMU-Authors

Aigner Ludwig
Couillard-Despr├ęs S├ębastien

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. Molecular Psychiatry (2009) 14, 856-864; doi: 10.1038/mp.2008.147; published online 13 January 2009


Useful keywords (using NLM MeSH Indexing)

Age Factors

Aging/physiology*

Animals

Animals, Newborn

Antidepressive Agents, Second-Generation/pharmacology*

Brain/cytology

Brain/drug effects

Brain/physiology*

Bromodeoxyuridine/metabolism

Cell Survival/drug effects

Fluoxetine/pharmacology*

Hippocampus/cytology

Hippocampus/drug effects

Male

Mice

Mice, Inbred C57BL

Nerve Tissue Proteins/metabolism

Neurogenesis/drug effects*

Neurons/drug effects*

Neurons/physiology


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antidepressant
neuronal survival
hippocampus
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mouse model