MicroRNA-34a Regulates the Depression-like Behavior in Mice by Modulating the Expression of Target Genes in the Dorsal Raphè
| Autor: | Rossella Ventura, Luisa Lo Iacono, Donald Ielpo, Alessandra Accoto, Tiziana Pascucci, Lucy Babicola, Diego Andolina, Sebastian Luca D'Addario, Fabio Ferlazzo, Matteo Di Segni |
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| Rok vydání: | 2019 |
| Předmět: |
Dorsal Raphe Nucleus
0301 basic medicine Ago2 Neuroscience (miscellaneous) RISC-Seq chronic stress depression-like behavior microRNA-34 raphe nuclei serotonin Biology Serotonergic 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Dorsal raphe nucleus Animals RNA-Induced Silencing Complex Chronic stress Mice Knockout Behavior Animal Depression Mechanism (biology) Phenotype Up-Regulation MicroRNAs 030104 developmental biology Gene Expression Regulation Neurology MicroRNA 34a Chronic Disease Serotonin Raphe nuclei Neuroscience Gene Deletion Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | Molecular Neurobiology. 57:823-836 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | Chronic stress exposure is known to increase vulnerability to the expression of psychiatric disorders, such as depression. Clinical and preclinical evidences support the involvement of the microRNA-34 family in stress-related psychiatric conditions and in the regulation of stress responses. However, the mechanism and the multiple targets by which the microRNA-34 family can affect the stress response and stress-related behavioral alteration are not fully known. Here, with the aid of constitutive and conditional genetic strategy, we examined the role of microRNA-34 family in the expression of depression-like phenotype in mice induced by chronic stress exposure, and we identified their "in vivo" targets during the stressful challenge. We found that microRNA-34a, under chronic stress, is significantly up-regulated in the mouse raphe nuclei, where its recruitment is necessary to induce depression-like behavioral alterations and impact the function of the serotonergic system. Moreover, by next-generation RNA-seq of Ago-2-bound mRNAs, we identified genes that are targeted by microRNA-34a in response to chronic stress and that are likely to mediate its effects. |
| Databáze: | OpenAIRE |
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