Dataset Information

Compromised Hippocampal Neuroplasticity in the Interferon-? and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

ABSTRACT: Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-? (IFN-?) 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-? and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-? 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-? 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 ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-? and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-? 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-? 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.

SUBMITTER: Sanchez-Mendoza EH

PROVIDER: S-EPMC7320059 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

Sanchez-Mendoza Eduardo H EH Camblor-Perujo Santiago S Martins Nascentes-Melo Luiza L Dzyubenko Egor E Fleischer Michael M Silva de Carvalho Tayana T Schmitt Linda-Isabell LI Leo Markus M Hagenacker Tim T Herring Arne A Keyvani Kathy K Bera Sujoy S Kononenko Natalia N Kleinschnitz Christoph C Hermann Dirk M DM

Molecular neurobiology 20200605 7

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:polycy ...[more]

PMID: 32504419

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Dataset Information

Compromised Hippocampal Neuroplasticity in the Interferon-? and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

Publications

Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

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