Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments
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(2020) 17:268
RESEARCH
Open Access
Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments Flora Reverchon1,2, Vidian de Concini1, Vanessa Larrigaldie1, Sulayman Benmerzoug1,3, Sylvain Briault1,4, Dieudonnée Togbé5, Bernhard Ryffel1, Valérie F. J. Quesniaux1 and Arnaud Menuet1*
Abstract Background: Interleukin (IL)-33 is expressed in a healthy brain and plays a pivotal role in several neuropathologies, as protective or contributing to the development of cerebral diseases associated with cognitive impairments. However, the role of IL-33 in the brain is poorly understood, raising the question of its involvement in immunoregulatory mechanisms. Methods: We administered recombinant IL-33 (rmIL-33) by intra-hippocampal injection to C57BL/6 J (WT) and IL1αβ deficient mice. Chronic minocycline administration was performed and cognitive functions were examined trough spatial habituation test. Hippocampal inflammatory responses were investigated by RT-qPCR. The microglia activation was assessed using immunohistological staining and fluorescence-activated cell sorting (FACS). Results: We showed that IL-33 administration in mice led to a spatial memory performance defect associated with an increase of inflammatory markers in the hippocampus while minocycline administration limited the inflammatory response. Quantitative assessment of glial cell activation in situ demonstrated an increase of proximal intersections per radius in each part of the hippocampus. Moreover, rmIL-33 significantly promoted the outgrowth of microglial processes. Fluorescence-activated cell sorting analysis on isolated microglia, revealed overexpression of IL-1β, 48 h post-rmIL-33 administration. This microglial reactivity was closely related to the onset of cognitive disturbance. Finally, we demonstrated that IL-1αβ deficient mice were resistant to cognitive disorders after intrahippocampal IL-33 injection. Conclusion: Thus, hippocampal IL-33 induced an inflammatory state, including IL-1β overexpression by microglia cells, being causative of the cognitive impairment. These results highlight the pathological role for IL-33 in the central nervous system, independently of a specific neuropathological model. Keywords: Interleukin-33, Interleukin-1, Microglia, Memory
* Correspondence: [email protected] Flora Reverchon and Vidian de Concini are co-first authors. 1 UMR7355, Experimental and Molecular Immunology and Neurogenetics, CNRS and University of Orléans, 3B rue de la Ferollerie, 45071 Orléans, France Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in
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