Pierre De Rossi, Eva Harde, Julien P. Dupuis, Laurent Martin, Naura Chounlamountri, Manon Bardin, Chantal Watrin, Claire Benetollo, Karin Pernet-Gallay, Heiko Luhmann, Jérôme Honnorat, Gael Malleret, Laurent Groc, Amparo Acker-Palmer, Paul Antoine Salin, Claire Meissirel
- Vascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic transmission and plasticity. VEGF increases the postsynaptic responses mediated by the N-methyl-d-aspartate type of glutamate receptors (GluNRs) in hippocampal neurons. This is concurrent with the formation of new synapses and with the synaptic recruitment of GluNR expressing the GluN2B subunit (GluNR-2B). VEGF induces a rapid redistribution of GluNR-2B at synaptic sites by increasing the surface dynamics of these receptors within the membrane. Consistently, silencing the expression of the VEGF receptor 2 (VEGFR2) in neural cells impairs hippocampal-dependent synaptic plasticity and consolidation of emotional memory. These findings demonstrated the direct implication of VEGF signaling in neurons via VEGFR2 in proper synaptic function. They highlight the potential of VEGF as a key regulator of GluNR synaptic function and suggest a role for VEGF in new therapeutic approaches targeting GluNR in depression.
MetadatenAuthor: | Pierre De Rossi, Eva Harde, Julien P. Dupuis, Laurent Martin, Naura Chounlamountri, Manon Bardin, Chantal Watrin, Claire Benetollo, Karin Pernet-Gallay, Heiko Luhmann, Jérôme Honnorat, Gael Malleret, Laurent Groc, Amparo Acker-PalmerORCiDGND, Paul Antoine Salin, Claire Meissirel |
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URN: | urn:nbn:de:hebis:30:3-439296 |
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DOI: | https://doi.org/10.1038/mp.2015.195 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26728568 |
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Parent Title (English): | Molecular psychiatry |
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Publisher: | Springer Nature |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/01/05 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/11/06 |
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Volume: | 21 |
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Page Number: | 13 |
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First Page: | 1768 |
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Last Page: | 1780 |
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Note: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if thematerial is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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HeBIS-PPN: | 42532513X |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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