Journal Article

Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation

Eichler, Amelie, Maggio, Nicola, Rodriguez-Rozada, Silvia, Strehl, Andreas, Waisman, Ari, Lenz, Maximilian, Jung, Steffen, Vlachos, Andreas, Frank, Stefan, Yogev, Nir, Kruse, Pia, Goren, Itamar, Deller, Thomas

2020

Overview

Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [ C57BL/6-Tg(TNFa-eGFP) ] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animal welfare / Animals / Artificial chromosomes / Cloning / Cytokines / Genes, Reporter / Hippocampal plasticity / Hippocampus / Hippocampus - metabolism / Hippocampus - physiology / Hippocampus - radiation effects / Immunology / Inflammation / Inflammation - metabolism / Interferon-gamma - metabolism / Interleukin 10 / Interleukin-10 - metabolism / Interleukin-10 - pharmacology / Interleukin-1beta - metabolism / Interleukin-6 - metabolism / Learning / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Long-term potentiation / Mice / Mice, Inbred C57BL / Mice, Transgenic / Microglia - metabolism / neuroinflammation / Neuronal Plasticity - drug effects / Neuronal Plasticity - physiology / Neuronal Plasticity - radiation effects / Neurons - metabolism / Neurons - physiology / Neurotransmission / non-invasive brain stimulation / Organoids / Penicillin / Pyramidal cells / Synaptic plasticity / Synaptic Transmission - physiology / Synaptic Transmission - radiation effects / TNFα-reporter mouse / Transcranial Magnetic Stimulation / Transgenic mice / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α / γ-Interferon