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Title: Langat virus infection affects hippocampal neuron morphology and function in mice without disease signs
Author(s): Cornelius, Angela D. A.
Hosseini, Shirin
Schreier, SarahLook up in the Integrated Authority File of the German National Library
Fritzsch, David
Weichert, Loreen
Michaelsen-Preusse, Kristin
Fendt, MarkusLook up in the Integrated Authority File of the German National Library
Kröger, AndreaLook up in the Integrated Authority File of the German National Library
Issue Date: 2020
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-845876
Subjects: Tick-borne encephalitis virus
Langat virus
Type I interferon
Inapparent infection
Learning and memory
Abstract: Background: 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. Methods: To compare the effect of low and high viral replication in the brain, wildtype and Irf-7−/− 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. Results: In contrast to susceptible Irf-7−/− mice, wildtype mice showed no disease signs upon LGTV infection. Detection of viral RNA in the olfactory bulb revealed CNS infections in wildtype and Irf-7−/− 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 Irf-7−/− 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. Conclusion: 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.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Projekt DEAL 2020
Journal Title: Journal of neuroinflammation
Publisher: BioMed Central
Publisher Place: London
Volume: 17
Issue: 2020
Original Publication: 10.1186/s12974-020-01951-w
Page Start: 1
Page End: 18
Appears in Collections:Medizinische Fakultät (OA)

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