Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine |
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| Affiliation: | 1. Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland;2. Department of Behavioral Neuroscience & Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland;3. Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;4. Department of Biological Psychology, University of Finance and Management in Warsaw, 01-030 Warsaw, Poland;5. Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland;1. Institute of Biomedicine and Translational Medicine, Department of Pharmacology, University of Tartu, 50411 Tartu, Estonia;2. Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, Finland;3. Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia;1. Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013, China;2. Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101, China;3. Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700, China;4. Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101, China;5. Department of Anesthesiology, Armed Police General Hospital, Beijing 100039, China;6. Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China |
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| Abstract: | The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. |
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| Keywords: | Adult neurogenesis Dentate gyrus Depression-like behavior Fluoxetine Stress |
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