Sanchez-Mendoza, Eduardo H., Camblor-Perujo, Santiago, Nascentes-Melo, Luiza Martins, Dzyubenko, Egor, Fleischer, Michael, de Carvalho, Tayana Silva, Schmitt, Linda-Isabell, Leo, Markus, Hagenacker, Tim, Herring, Arne, Keyvani, Kathy, Bera, Sujoy, Kononenko, Natalia, Kleinschnitz, Christoph and Hermann, Dirk M. (2020). Compromised Hippocampal Neuroplasticity in the Interferon-alpha and Toll-like Receptor-3 Activation-Induced Mouse Depression Model. Mol. Neurobiol., 57 (7). S. 3171 - 3183. NEW YORK: SPRINGER. ISSN 1559-1182
Full text not available from this repository.Abstract
Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-alpha (IFN-alpha) potentiates immune responses against viral pathogens that induce toll-like receptor-3 (TLR3) activation but evokes severe major depressive disorder in humans by mechanisms that remain insufficiently described. By using a previously established mouse model of depression induced by combined delivery of IFN-alpha and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-alpha and poly(I:C) reduce apical dendritic spine density in the hippocampal CA1 area ex vivo via mechanisms involving decreased TrkB signaling. In vitro, IFN-alpha and poly(I:C) treatments required neuronal activity to reduce dendritic spine density and TrkB signaling. The levels of presynaptic protein vesicular glutamate transporter (VGLUT)-1 and postsynaptic protein postsynaptic density-95 (PSD95) were specifically decreased, whereas the expression of both synaptic and extrasynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-alpha and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-alpha and poly(I:C) costimulation were accompanied by an increased action potential threshold and action potential frequency, indicative of impaired neuronal excitability. Taken together, IFN-alpha and poly(I:C) delivery leads to structural and functional alterations at the synapse indicating that compromised neuroplasticity may play an integral role in the pathogenesis of immune response-induced depression.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-330552 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1007/s12035-020-01927-0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Mol. Neurobiol. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 57 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Number: | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Page Range: | S. 3171 - 3183 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2020 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | SPRINGER | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1559-1182 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/33055 |
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