A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories
| Autor: | Farahnaz Sananbenesi, Susanne Burkhardt, Kim Blom, Jessica Wittnam, Lennart Opitz, Athanasios Zovoilis, Gabriella Salinas-Riester, Andre Fischer, Roberto Carlos Agis-Balboa, Nambirajan Govindarajan, Ulla Haladyniak, Dario Arcos-Diaz, Hope Y Agbemenyah |
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| Rok vydání: | 2011 |
| Předmět: |
Fear processing in the brain
0303 health sciences endocrine system diseases General Immunology and Microbiology IGFBP7 General Neuroscience Neurogenesis social sciences Extinction (psychology) Hippocampal formation Biology Stimulus (physiology) humanities General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Signal transduction Molecular Biology Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | The EMBO Journal. 30:4071-4083 |
| ISSN: | 0261-4189 |
| Popis: | Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin‐growth factor 2 ( Igf2 ) and downregulation of insulin‐growth factor binding protein 7 ( Igfbp7 ). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2‐dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinction‐induced IGF2/IGFBP7 signalling promotes the survival of 17–19‐day‐old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. |
| Databáze: | OpenAIRE |
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