Activating newborn neurons suppresses depression and anxiety-like behaviors
| Autor: | Yiwen Zhu, Elif Tunc-Ozcan, John A. Kessler, Chian Yu Peng, Sara R. Dunlop, Anis Contractor |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Science Neurogenesis General Physics and Astronomy Mice Transgenic 02 engineering and technology Hippocampal formation Anxiety Hippocampus General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice Fluoxetine medicine Premovement neuronal activity Animals lcsh:Science Neurons Depressive Disorder Major Multidisciplinary Behavior Animal Molecular medicine business.industry Depression Dentate gyrus General Chemistry Chemogenetics 021001 nanoscience & nanotechnology medicine.disease Antidepressive Agents 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Dentate Gyrus Major depressive disorder Antidepressant lcsh:Q Female 0210 nano-technology business Neuroscience medicine.drug |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2041-1723 |
| Popis: | The etiology of major depressive disorder (MDD), the leading cause of worldwide disability, is unknown. The neurogenic hypothesis proposes that MDD is linked to impairments of adult neurogenesis in the hippocampal dentate gyrus (DG), while the effects of antidepressants are mediated by increased neurogenesis. However, alterations in neurogenesis and endophenotypes are not always causally linked, and the relationship between increased neurogenesis and altered behavior is controversial. To address causality, we used chemogenetics in transgenic mice to selectively manipulate activity of newborn DG neurons. Suppressing excitability of newborn neurons without altering neurogenesis abolish the antidepressant effects of fluoxetine. Remarkably, activating these neurons is sufficient to alleviate depression-like behavior and reverse the adverse effects of unpredictable chronic mild stress. Our results demonstrate a direct causal relationship between newborn neuronal activity and affective behavior. Thus, strategies that target not only neurogenesis but also activity of newborn neurons may lead to more effective antidepressants. It is unclear if there is a causal link between increased neurogenesis and altered affective behaviors in major depressive disorders. Here, the authors show that selectively suppressing the excitability of newborn neurons, without altering neurogenesis, abolishes the antidepressant effects of fluoxetine. |
| Databáze: | OpenAIRE |
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