{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:19:47Z","timestamp":1790763587956,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB854\/AK"],"award-info":[{"award-number":["SFB854\/AK"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KI1728H"],"award-info":[{"award-number":["01KI1728H"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmholtz Zentrum f\u00fcr Infektionsfoschung","award":["HIRSIB"],"award-info":[{"award-number":["HIRSIB"]}]},{"name":"Federal state of Saxony-Anhalt and the European Structural and Investmant Funds","award":["ESF ZS\/2016\/08\/80645"],"award-info":[{"award-number":["ESF ZS\/2016\/08\/80645"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause the serious illness tick-borne encephalitis (TBE). Patients with clinical symptoms can suffer from severe meningoencephalitis with sequelae that include cognitive disorders and paralysis. While less than 30% of patients with clinical symptoms develop meningoencephalitis, the number of seropositive individuals in some regions indicates a much higher prevalence of TBEV infections, either with no or subclinical symptoms. The functional relevance of these subclinical TBEV infections and their influence on brain functions, such as learning and memory, has not been investigated so far.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To compare the effect of low and high viral replication in the brain, wildtype and <jats:italic>Irf-7<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were infected with Langat virus (LGTV), which belongs to the TBEV-serogroup. The viral burden was analyzed in the olfactory bulb and the hippocampus. Open field, elevated plus maze, and Morris water maze experiments were performed to determine the impact on anxiety-like behavior, learning, and memory formation. Spine density of hippocampal neurons and activation of microglia and astrocytes were analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In contrast to susceptible <jats:italic>Irf-7<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, wildtype mice showed no disease signs upon LGTV infection. Detection of viral RNA in the olfactory bulb revealed CNS infections in wildtype and <jats:italic>Irf-7<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Very low levels of viral replication were detectable in the hippocampus of wildtype mice. Although wildtype mice develop no disease signs, they showed reduced anxiety-like behavior and impaired memory formation, whereas <jats:italic>Irf-7<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were not affected. This impairment was associated with a significant decrease in spine density of neurons in the hippocampal CA1 region of wildtype mice. Microglia activation and astrogliosis were detected in the hippocampus.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this study, we demonstrate that subclinical infections by viruses from the TBEV-serogroup affected anxiety-like behavior. Virus replication in the olfactory bulb induced far-reaching effects on hippocampal neuron morphology and impaired hippocampus-dependent learning and memory formation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-020-01951-w","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T17:02:32Z","timestamp":1600621352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Langat virus infection affects hippocampal neuron morphology and function in mice without disease signs"],"prefix":"10.1186","volume":"17","author":[{"given":"Angela D. A.","family":"Cornelius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schreier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fritzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreen","family":"Weichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Michaelsen-Preusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Fendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-8711","authenticated-orcid":false,"given":"Andrea","family":"Kr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"1951_CR1","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.virol.2006.09.015","volume":"361","author":"G Grard","year":"2007","unstructured":"Grard G, Moureau G, Charrel RN, Lemasson JJ, Gonzalez JP, Gallian P, Gritsun TS, Holmes EC, Gould EA, de Lamballerie X. Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy. Virology. 2007;361:80\u201392.","journal-title":"Virology"},{"key":"1951_CR2","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/S0140-6736(08)60800-4","volume":"371","author":"L Lindquist","year":"2008","unstructured":"Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008;371:1861\u201371.","journal-title":"Lancet"},{"key":"1951_CR3","doi-asserted-by":"crossref","unstructured":"Brockmann SO, Oehme R, Buckenmaier T, Beer M, Jeffery-Smith A, Spannenkrebs M, Haag-Milz S, Wagner-Wiening C, Schlegel C, Fritz J, et al. A cluster of two human cases of tick-borne encephalitis (TBE) transmitted by unpasteurised goat milk and cheese in Germany. Euro Surveill 2018. 2016:23.","DOI":"10.2807\/1560-7917.ES.2018.23.15.17-00336"},{"key":"1951_CR4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3109\/00365549609027160","volume":"28","author":"M Haglund","year":"1996","unstructured":"Haglund M, Forsgren M, Lindh G, Lindquist L. A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature: need for a vaccination strategy. Scand J Infect Dis. 1996;28:217\u201324.","journal-title":"Scand J Infect Dis"},{"key":"1951_CR5","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1086\/342059","volume":"35","author":"A Mickiene","year":"2002","unstructured":"Mickiene A, Laiskonis A, Gunther G, Vene S, Lundkvist A, Lindquist L. Tickborne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis. 2002;35:650\u20138.","journal-title":"Clin Infect Dis"},{"issue":"Pt 11","key":"1951_CR6","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1093\/brain\/122.11.2067","volume":"122","author":"R Kaiser","year":"1999","unstructured":"Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients. Brain. 1999;122(Pt 11):2067\u201378.","journal-title":"Brain"},{"key":"1951_CR7","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1007\/s004150050077","volume":"244","author":"G Gunther","year":"1997","unstructured":"Gunther G, Haglund M, Lindquist L, Forsgren M, Skoldenberg B. Tick-bone encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome. J Neurol. 1997;244:230\u20138.","journal-title":"J Neurol"},{"key":"1951_CR8","doi-asserted-by":"publisher","first-page":"12202","DOI":"10.1128\/JVI.01215-14","volume":"88","author":"E Weber","year":"2014","unstructured":"Weber E, Finsterbusch K, Lindquist R, Nair S, Lienenklaus S, Gekara NO, Janik D, Weiss S, Kalinke U, Overby AK, Kroger A. Type I interferon protects mice from fatal neurotropic infection with Langat virus by systemic and local antiviral responses. J Virol. 2014;88:12202\u201312.","journal-title":"J Virol"},{"key":"1951_CR9","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/nature03464","volume":"434","author":"K Honda","year":"2005","unstructured":"Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005;434:772\u20137.","journal-title":"Nature"},{"key":"1951_CR10","doi-asserted-by":"publisher","first-page":"10709","DOI":"10.1523\/JNEUROSCI.3376-06.2006","volume":"26","author":"NL Sparkman","year":"2006","unstructured":"Sparkman NL, Buchanan JB, Heyen JR, Chen J, Beverly JL, Johnson RW. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. J Neurosci. 2006;26:10709\u201316.","journal-title":"J Neurosci"},{"key":"1951_CR11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nrn2297","volume":"9","author":"R Dantzer","year":"2008","unstructured":"Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46\u201356.","journal-title":"Nat Rev Neurosci"},{"key":"1951_CR12","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","volume":"25","author":"R Yirmiya","year":"2011","unstructured":"Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun. 2011;25:181\u2013213.","journal-title":"Brain Behav Immun"},{"key":"1951_CR13","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.immuni.2016.04.005","volume":"44","author":"T Blank","year":"2016","unstructured":"Blank T, Detje CN, Spiess A, Hagemeyer N, Brendecke SM, Wolfart J, Staszewski O, Zoller T, Papageorgiou I, Schneider J, et al. Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment. Immunity. 2016;44:901\u201312.","journal-title":"Immunity"},{"key":"1951_CR14","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1046\/j.1460-9568.2002.02012.x","volume":"15","author":"AM Lynch","year":"2002","unstructured":"Lynch AM, Lynch MA. The age-related increase in IL-1 type I receptor in rat hippocampus is coupled with an increase in caspase-3 activation. Eur J Neurosci. 2002;15:1779\u201388.","journal-title":"Eur J Neurosci"},{"key":"1951_CR15","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0079-6123(07)63020-9","volume":"163","author":"M Pickering","year":"2007","unstructured":"Pickering M, O'Connor JJ. Pro-inflammatory cytokines and their effects in the dentate gyrus. Prog Brain Res. 2007;163:339\u201354.","journal-title":"Prog Brain Res"},{"key":"1951_CR16","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.neurobiolaging.2007.02.027","volume":"29","author":"L Tong","year":"2008","unstructured":"Tong L, Balazs R, Soiampornkul R, Thangnipon W, Cotman CW. Interleukin-1 beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol Aging. 2008;29:1380\u201393.","journal-title":"Neurobiol Aging"},{"key":"1951_CR17","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/35049004","volume":"2","author":"MM Poo","year":"2001","unstructured":"Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci. 2001;2:24\u201332.","journal-title":"Nat Rev Neurosci"},{"key":"1951_CR18","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1101\/lm.51202","volume":"9","author":"WJ Tyler","year":"2002","unstructured":"Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002;9:224\u201337.","journal-title":"Learn Mem"},{"key":"1951_CR19","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nrn2738","volume":"10","author":"L Minichiello","year":"2009","unstructured":"Minichiello L. TrkB signalling pathways in LTP and learning. Nat Rev Neurosci. 2009;10:850\u201360.","journal-title":"Nat Rev Neurosci"},{"key":"1951_CR20","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1523\/JNEUROSCI.1740-17.2018","volume":"38","author":"S Hosseini","year":"2018","unstructured":"Hosseini S, Wilk E, Michaelsen-Preusse K, Gerhauser I, Baumgartner W, Geffers R, Schughart K, Korte M. Long-term neuroinflammation induced by influenza a virus infection and the impact on hippocampal neuron morphology and function. J Neurosci. 2018;38:3060\u201380.","journal-title":"J Neurosci"},{"key":"1951_CR21","doi-asserted-by":"publisher","first-page":"553","DOI":"10.33549\/physiolres.933480","volume":"66","author":"R Zakaria","year":"2017","unstructured":"Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B. Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer\u2019s disease. Physiol Res. 2017;66:553\u201365.","journal-title":"Physiol Res"},{"key":"1951_CR22","doi-asserted-by":"publisher","first-page":"8470","DOI":"10.1128\/JVI.00176-10","volume":"84","author":"AK Overby","year":"2010","unstructured":"Overby AK, Popov VL, Niedrig M, Weber F. Tick-borne encephalitis virus delays interferon induction and hides its double-stranded RNA in intracellular membrane vesicles. J Virol. 2010;84:8470\u201383.","journal-title":"J Virol"},{"key":"1951_CR23","first-page":"141","volume":"38","author":"M Niedrig","year":"1994","unstructured":"Niedrig M, Klockmann U, Lang W, Roeder J, Burk S, Modrow S, Pauli G. Monoclonal antibodies directed against tick-borne encephalitis virus with neutralizing activity in vivo. Acta Virol. 1994;38:141\u20139.","journal-title":"Acta Virol"},{"key":"1951_CR24","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1037\/0033-2909.83.3.482","volume":"83","author":"RN Walsh","year":"1976","unstructured":"Walsh RN, Cummins RA. The open-field test: a critical review. Psychol Bull. 1976;83:482\u2013504.","journal-title":"Psychol Bull"},{"key":"1951_CR25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/0091-3057(95)02126-4","volume":"54","author":"S Hogg","year":"1996","unstructured":"Hogg S. A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav. 1996;54:21\u201330.","journal-title":"Pharmacol Biochem Behav"},{"key":"1951_CR26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","volume":"11","author":"R Morris","year":"1984","unstructured":"Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11:47\u201360.","journal-title":"J Neurosci Methods"},{"key":"1951_CR27","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/nprot.2006.116","volume":"1","author":"CV Vorhees","year":"2006","unstructured":"Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1:848\u201358.","journal-title":"Nat Protoc"},{"key":"1951_CR28","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.bbr.2004.04.013","volume":"155","author":"IQ Whishaw","year":"2004","unstructured":"Whishaw IQ. Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus non-spatial behavior. Behav Brain Res. 2004;155:177\u201384.","journal-title":"Behav Brain Res"},{"key":"1951_CR29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fnins.2013.00063","volume":"7","author":"A Garthe","year":"2013","unstructured":"Garthe A, Kempermann G. An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis. Front Neurosci. 2013;7:63.","journal-title":"Front Neurosci"},{"key":"1951_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005464","volume":"4","author":"A Garthe","year":"2009","unstructured":"Garthe A, Behr J, Kempermann G. Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One. 2009;4:e5464.","journal-title":"PLoS One"},{"key":"1951_CR31","doi-asserted-by":"crossref","unstructured":"Seibenhener ML, Wooten MC. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015:e52434.","DOI":"10.3791\/52434"},{"key":"1951_CR32","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nprot.2007.44","volume":"2","author":"AA Walf","year":"2007","unstructured":"Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2:322\u20138.","journal-title":"Nat Protoc"},{"key":"1951_CR33","doi-asserted-by":"publisher","first-page":"12673","DOI":"10.1073\/pnas.91.26.12673","volume":"91","author":"MB Moser","year":"1994","unstructured":"Moser MB, Trommald M, Andersen P. An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc Natl Acad Sci U S A. 1994;91:12673\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1951_CR34","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3389\/fnbeh.2014.00112","volume":"8","author":"A Adhikari","year":"2014","unstructured":"Adhikari A. Distributed circuits underlying anxiety. Front Behav Neurosci. 2014;8:112.","journal-title":"Front Behav Neurosci"},{"key":"1951_CR35","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1148\/radiol.2492071917","volume":"249","author":"JM Provenzale","year":"2008","unstructured":"Provenzale JM, vanLandingham KE, Lewis DV, Mukundan S Jr, White LE. Extrahippocampal involvement in human herpesvirus 6 encephalitis depicted at MR imaging. Radiology. 2008;249:955\u201363.","journal-title":"Radiology"},{"key":"1951_CR36","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.physbeh.2006.06.019","volume":"89","author":"M Lyte","year":"2006","unstructured":"Lyte M, Li W, Opitz N, Gaykema RPA, Goehler LE. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia citrobacter rodentium. Physiology Behavior. 2006;89:350\u20137.","journal-title":"Physiology Behavior"},{"key":"1951_CR37","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.1523\/JNEUROSCI.6389-11.2012","volume":"32","author":"HA Jurgens","year":"2012","unstructured":"Jurgens HA, Amancherla K, Johnson RW. Influenza infection induces neuroinflammation, alters hippocampal neuron morphology, and impairs cognition in adult mice. J Neurosci. 2012;32:3958\u201368.","journal-title":"J Neurosci"},{"key":"1951_CR38","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature18283","volume":"534","author":"MJ Vasek","year":"2016","unstructured":"Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A, Yu J, Perez-Torres C, Frouin A, Wilton DK, et al. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature. 2016;534:538\u201343.","journal-title":"Nature"},{"key":"1951_CR39","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1037\/a0025959","volume":"126","author":"T Eilam-Stock","year":"2012","unstructured":"Eilam-Stock T, Serrano P, Frankfurt M, Luine V. Bisphenol-A impairs memory and reduces dendritic spine density in adult male rats. Behav Neurosci. 2012;126:175\u201385.","journal-title":"Behav Neurosci"},{"key":"1951_CR40","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1037\/a0025770","volume":"126","author":"CD Conrad","year":"2012","unstructured":"Conrad CD, McLaughlin KJ, Huynh TN, El-Ashmawy M, Sparks M. Chronic stress and a cyclic regimen of estradiol administration separately facilitate spatial memory: relationship with hippocampal CA1 spine density and dendritic complexity. Behav Neurosci. 2012;126:142\u201356.","journal-title":"Behav Neurosci"},{"key":"1951_CR41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41590-017-0021-y","volume":"19","author":"C Garber","year":"2018","unstructured":"Garber C, Vasek MJ, Vollmer LL, Sun T, Jiang X, Klein RS. Astrocytes decrease adult neurogenesis during virus-induced memory dysfunction via IL-1. Nature immunology. 2018;19:151\u201361.","journal-title":"Nature immunology"},{"key":"1951_CR42","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.bbi.2012.11.013","volume":"28","author":"Y Diz-Chaves","year":"2013","unstructured":"Diz-Chaves Y, Astiz M, Bellini MJ, Garcia-Segura LM. Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice. Brain Behav Immun. 2013;28:196\u2013206.","journal-title":"Brain Behav Immun"},{"key":"1951_CR43","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1006\/cyto.1997.0290","volume":"10","author":"M Maes","year":"1998","unstructured":"Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine. 1998;10:313\u20138.","journal-title":"Cytokine"},{"key":"1951_CR44","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nrn3978","volume":"16","author":"ML Estes","year":"2015","unstructured":"Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci. 2015;16:469\u201386.","journal-title":"Nat Rev Neurosci"},{"key":"1951_CR45","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1101\/lm.028357.112","volume":"20","author":"I Marin","year":"2013","unstructured":"Marin I, Kipnis J. Learning and memory ... and the immune system. Learn Mem. 2013;20:601\u20136.","journal-title":"Learn Mem"},{"key":"1951_CR46","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.nlm.2014.08.008","volume":"115","author":"EJ Donzis","year":"2014","unstructured":"Donzis EJ, Tronson NC. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences. Neurobiol Learn Mem. 2014;115:68\u201377.","journal-title":"Neurobiol Learn Mem"},{"key":"1951_CR47","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12974-015-0244-5","volume":"12","author":"PK Chang","year":"2015","unstructured":"Chang PK, Khatchadourian A, McKinney RA, Maysinger D. Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology. J Neuroinflammation. 2015;12:34.","journal-title":"J Neuroinflammation"},{"key":"1951_CR48","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.immuni.2008.03.011","volume":"28","author":"M Prinz","year":"2008","unstructured":"Prinz M, Schmidt H, Mildner A, Knobeloch KP, Hanisch UK, Raasch J, Merkler D, Detje C, Gutcher I, Mages J, et al. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity. 2008;28:675\u201386.","journal-title":"Immunity"},{"key":"1951_CR49","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s00401-015-1418-z","volume":"130","author":"R Khorooshi","year":"2015","unstructured":"Khorooshi R, Morch MT, Holm TH, Berg CT, Dieu RT, Draeby D, Issazadeh-Navikas S, Weiss S, Lienenklaus S, Owens T. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis. Acta Neuropathol. 2015;130:107\u201318.","journal-title":"Acta Neuropathol"},{"key":"1951_CR50","doi-asserted-by":"publisher","first-page":"2906","DOI":"10.15252\/embj.201489293","volume":"33","author":"M Cohen","year":"2014","unstructured":"Cohen M, Matcovitch O, David E, Barnett-Itzhaki Z, Keren-Shaul H, Blecher-Gonen R, Jaitin DA, Sica A, Amit I, Schwartz M. Chronic exposure to TGFbeta1 regulates myeloid cell inflammatory response in an IRF7-dependent manner. Embo j. 2014;33:2906\u201321.","journal-title":"Embo j"},{"key":"1951_CR51","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.cell.2015.08.069","volume":"163","author":"P Ejlerskov","year":"2015","unstructured":"Ejlerskov P, Hultberg JG, Wang J, Carlsson R, Ambjorn M, Kuss M, Liu Y, Porcu G, Kolkova K, Friis Rundsten C, et al. Lack of neuronal IFN-beta-IFNAR causes Lewy body- and Parkinson\u2019s disease-like dementia. Cell. 2015;163:324\u201339.","journal-title":"Cell"},{"key":"1951_CR52","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41467-017-00769-0","volume":"8","author":"A Deczkowska","year":"2017","unstructured":"Deczkowska A, Matcovitch-Natan O, Tsitsou-Kampeli A, Ben-Hamo S, Dvir-Szternfeld R, Spinrad A, Singer O, David E, Winter DR, Smith LK, et al. Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner. Nat Commun. 2017;8:717.","journal-title":"Nat Commun"},{"key":"1951_CR53","doi-asserted-by":"crossref","unstructured":"Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, Berkutzki T, Barnett-Itzhaki Z, Bezalel D, Wyss-Coray T, et al: Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 2014, 346:89-93.","DOI":"10.1126\/science.1252945"},{"key":"1951_CR54","doi-asserted-by":"publisher","first-page":"107666","DOI":"10.1016\/j.celrep.2020.107666","volume":"31","author":"S Hosseini","year":"2020","unstructured":"Hosseini S, Michaelsen-Preusse K, Grigoryan G, Chhatbar C, Kalinke U, Korte M. Type I interferon receptor signaling in astrocytes regulates hippocampal synaptic plasticity and cognitive function of the healthy CNS. Cell Rep. 2020;31:107666.","journal-title":"Cell Rep"},{"key":"1951_CR55","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nn.3641","volume":"17","author":"Y Zhan","year":"2014","unstructured":"Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, Gross CT. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci. 2014;17:400\u20136.","journal-title":"Nat Neurosci"},{"key":"1951_CR56","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","volume":"155","author":"CN Parkhurst","year":"2013","unstructured":"Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. 2013;155:1596\u2013609.","journal-title":"Cell"},{"key":"1951_CR57","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1126\/science.1202529","volume":"333","author":"RC Paolicelli","year":"2011","unstructured":"Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333:1456\u20138.","journal-title":"Science"},{"key":"1951_CR58","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","volume":"74","author":"DP Schafer","year":"2012","unstructured":"Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74:691\u2013705.","journal-title":"Neuron"},{"key":"1951_CR59","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41593-019-0427-y","volume":"22","author":"C Garber","year":"2019","unstructured":"Garber C, Soung A, Vollmer LL, Kanmogne M, Last A, Brown J, Klein RS. T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses. Nature neuroscience. 2019;22:1276\u201388.","journal-title":"Nature neuroscience"},{"key":"1951_CR60","doi-asserted-by":"publisher","first-page":"e1007617","DOI":"10.1371\/journal.ppat.1007617","volume":"15","author":"G De Chiara","year":"2019","unstructured":"De Chiara G, Piacentini R, Fabiani M, Mastrodonato A, Marcocci ME, Limongi D, Napoletani G, Protto V, Coluccio P, Celestino I, et al. Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLoS pathogens. 2019;15:e1007617.","journal-title":"PLoS pathogens"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01951-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01951-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01951-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T01:16:10Z","timestamp":1650244570000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01951-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,20]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1951"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01951-w","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,20]]},"assertion":[{"value":"19 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were performed in compliance with the animal welfare law (EU-Directive 2010\/63\/EU). The mice were housed and handled in accordance with good animal practice as defined by FELASA. All animal experiments were approved by the Lower Saxony State Office of Consumer Protection and Food Safety under permit number AZ 33.9-42502-04-15\/1950 or by the Landesverwaltungsamt Sachsen-Anhalt AZ 42502-2-1344, University Magdeburg.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"278"}}