Universität zu Köln

Lenz, Maximilian, Eichler, Amelie, Kruse, Pia, Strehl, Andreas, Rodriguez-Rozada, Silvia, Goren, Itamar, Yogev, Nir, Frank, Stefan, Waisman, Ari, Deller, Thomas, Jung, Steffen, Maggio, Nicola and Vlachos, Andreas (2020). Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation. Front. Immunol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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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 [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNF alpha) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNF alpha, IL6, IL1 beta, and IFN gamma 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lenz, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichler, Amelie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kruse, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Strehl, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodriguez-Rozada, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Goren, Itamar UNSPECIFIED UNSPECIFIED UNSPECIFIED Yogev, Nir UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED UNSPECIFIED UNSPECIFIED Deller, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Jung, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Maggio, Nicola UNSPECIFIED UNSPECIFIED UNSPECIFIED Vlachos, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-307887
DOI:	10.3389/fimmu.2020.614509
Journal or Publication Title:	Front. Immunol.
Volume:	11
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LONG-TERM POTENTIATION; TOLL-LIKE RECEPTOR-4; EXCITATORY POSTSYNAPSES; TNF-ALPHA; MICROGLIA; INFLAMMATION; EXPRESSION; NEUROINFLAMMATION; CYTOKINES; TMS Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30788