Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation
Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation
ABSTRACT 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 [C57BL6-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.
Waisman Ari、Yogev Nir、Rodriguez-Rozada Silvia、Frank Stefan、Maggio Nicola、Vlachos Andreas、Kruse Pia、Goren Itamar、Lenz Maximilian、Strehl Andreas、Jung Steffen、Deller Thomas、Eichler Amelie
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University MainzInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz||Experimental Immunology, Department of Dermatology, University Medical Center CologneInstitute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University FrankfurtPharmazentrum Frankfurt/ZAFES, Goethe-University FrankfurtDepartment of Neurology and Sagol Center for Neurosciences, Talpiot Medical Leadership Program, The Chaim Sheba Medical Center||Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv UniversityDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg||Center Brain Links Brain Tools, University of Freiburg||Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of FreiburgDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgPharmazentrum Frankfurt/ZAFES, Goethe-University FrankfurtDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgInstitute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University FrankfurtDepartment of Immunology, Weizmann Institute of ScienceInstitute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University FrankfurtDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg
基础医学神经病学、精神病学生物科学研究方法、生物科学研究技术
synaptic plasticityneuroinflammationnon-invasive brain stimulationtranscranial magnetic stimulation (TMS)TNFα-reporter mouse
Waisman Ari,Yogev Nir,Rodriguez-Rozada Silvia,Frank Stefan,Maggio Nicola,Vlachos Andreas,Kruse Pia,Goren Itamar,Lenz Maximilian,Strehl Andreas,Jung Steffen,Deller Thomas,Eichler Amelie.Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation[EB/OL].(2025-03-28)[2025-05-22].https://www.biorxiv.org/content/10.1101/2020.10.16.336065.点此复制
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