Markus Petermann1,2, Golo Kronenberg3,4, Valentina Mosienko1,5, Michael Bader1,2,6,7,8, Natalia Alenina1,7,9, Rainer Hellweg4, Friederike Klempin1,2,4. 1. Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany. 2. Berlin Institute of Health, Berlin, Germany. 3. University of Leicester and Leicestershire Partnership NHS Trust, Leicester, UK. 4. Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Berlin, Germany. 5. current address: University of Exeter, College of Medicine and Health, EX4 4PS, Exeter, UK. 6. Charité-University Medicine Berlin, Berlin, Germany. 7. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany. 8. University of Lübeck, Lübeck, Germany. 9. Institute of Cytology, Russian Academy of Science, St. Petersburg, Russia.
Abstract
INTRODUCTION: Brain-derived neurotrophic factor (BDNF) has been implicated in the pro-neurogenic effect of selective serotonin reuptake inhibitors. In this study, we used Tph2 -/- mice lacking brain serotonin to dissect the interplay between BDNF and the serotonin system in mediating the effects of antidepressant pharmacotherapy on adult neurogenesis in the hippocampus. METHODS: Besides citalopram (CIT), we tested tianeptine (TIA), an antidepressant whose mechanism of action is not well understood. Specifically, we examined cell survival and endogenous concentrations of BDNF following daily injection of the drugs. RESULTS: Twenty-one days of CIT, but not of TIA, led to a significant increase in the survival of newly generated cells in the dentate gyrus of wild-type mice, without a significant effect on BDNF protein levels by either treatment. In Tph2 -/- mice, adult neurogenesis was consistently increased. Furthermore, Tph2 -/- mice showed increased BDNF protein levels, which were not affected by TIA but were significantly reduced by CIT. DISCUSSION: We conclude that the effects of CIT on adult neurogenesis are not explained by changes in BDNF protein concentrations in the hippocampus. Thieme. All rights reserved.
INTRODUCTION:Brain-derived neurotrophic factor (BDNF) has been implicated in the pro-neurogenic effect of selective serotonin reuptake inhibitors. In this study, we used Tph2 -/- mice lacking brain serotonin to dissect the interplay between BDNF and the serotonin system in mediating the effects of antidepressant pharmacotherapy on adult neurogenesis in the hippocampus. METHODS: Besides citalopram (CIT), we tested tianeptine (TIA), an antidepressant whose mechanism of action is not well understood. Specifically, we examined cell survival and endogenous concentrations of BDNF following daily injection of the drugs. RESULTS: Twenty-one days of CIT, but not of TIA, led to a significant increase in the survival of newly generated cells in the dentate gyrus of wild-type mice, without a significant effect on BDNF protein levels by either treatment. In Tph2 -/- mice, adult neurogenesis was consistently increased. Furthermore, Tph2 -/- mice showed increased BDNF protein levels, which were not affected by TIA but were significantly reduced by CIT. DISCUSSION: We conclude that the effects of CIT on adult neurogenesis are not explained by changes in BDNF protein concentrations in the hippocampus. Thieme. All rights reserved.