Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model
Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-α (IFN-α) 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-α and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-α 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-α 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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-α and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-α 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-α 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Molecular neurobiology - 57(2020), 7 vom: 05. Juli, Seite 3171-3182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sanchez-Mendoza, Eduardo H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.05.2021 Date Revised 19.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12035-020-01927-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310839548 |
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| 245 | 1 | 0 | |a Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-α (IFN-α) 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-α and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-α 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-α 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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-α and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-α 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-α 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dendritic plasticity | |
| 650 | 4 | |a Major depressive disorder | |
| 650 | 4 | |a Neuronal depolarization | |
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| 650 | 4 | |a Patch clamp recording | |
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| 700 | 1 | |a Martins Nascentes-Melo, Luiza |e verfasserin |4 aut | |
| 700 | 1 | |a Dzyubenko, Egor |e verfasserin |4 aut | |
| 700 | 1 | |a Fleischer, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Silva de Carvalho, Tayana |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitt, Linda-Isabell |e verfasserin |4 aut | |
| 700 | 1 | |a Leo, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Hagenacker, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Herring, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Keyvani, Kathy |e verfasserin |4 aut | |
| 700 | 1 | |a Bera, Sujoy |e verfasserin |4 aut | |
| 700 | 1 | |a Kononenko, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Kleinschnitz, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Hermann, Dirk M |e verfasserin |4 aut | |
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