Neurotrophic viral infections represent a major inflammatory stimulus, which severely affects neural circuits. The clinical manifestation of viral infections ranges from clinical inapparent to fatal conditions that lead to persistent disabilities or death. In this research focus, we will assess the mechanisms of neurovirulence, viral spread, and synaptic dysfunction following viral infections of the brain. Together with our collaborating partners, we ultimately aim at providing novel therapeutic strategies for acute and chronic neurotrophic viral infections.

Viruses, including Venezolean Equine Encephalitis Virus (VEEV), Herpes simplex virus (HSV), Cytomegalie Virus (CMV), and SARS-CoV-2 target a variety of cell types in the CNS. Our experimental strategies will test for infection-induced synaptic plasticity, which presumably cause maladaptive changes in neural circuits. Here, tissue cultures are suitable in vitro models that allow for experimental strategies covering long time scales. Moreover, environmental and intrinsic determinants of viral reactivation will be studied with respect to cellular interactions in tissue of the central nervous system.

Experimental methods:

• Organotypic brain tissue cultures
• Single-cell whole-cell patch-clamp recordings
• High-resolution confocal microscopy, synaptic microarchitecture
• Electron Microscopy
• Cytokine profiling
• Single-nuclei sequencing
• Crispr/Cas genetic engineering

Collaborating Partners:

Prof. Dr. Lars Dölken (Institute of Virology, MHH)

Prof. Dr. Gisa Gerold (Institute of Virology, University of Innsbruck)

Prof. Dr. Ulrich Kalinke (Twincore)

For collaboration requests, please contact Dr. Amelie Eichler (Group Leader, Eichler.Amelie@mh-hannover.de) and Prof. Dr. Maximilian Lenz (neuroanatomie@mh-hannover.de).

Key publications:

Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation. Eichler A, Kleidonas D, Turi Z, Fliegauf M, Kirsch M, Pfeifer D, Masuda T, Prinz M, Lenz M, Vlachos A. J Neurosci. 2023 Apr 26;43(17):3042-3060. doi: 10.1523/JNEUROSCI.2226-22.2023. Epub 2023 Mar 28.

Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation. Lenz M, Eichler A, Kruse P, Strehl A, Rodriguez-Rozada S, Goren I, Yogev N, Frank S, Waisman A, Deller T, Jung S, Maggio N, Vlachos A. Front Immunol. 2020 Dec 16;11:614509. doi: 10.3389/fimmu.2020.614509. eCollection 2020.

Denervated mouse dentate granule cells adjust their excitatory but not inhibitory synapses following in vitro entorhinal cortex lesion. Lenz M, Galanis C, Kleidonas D, Fellenz M, Deller T, Vlachos A. Exp Neurol. 2019 Feb;312:1-9. doi: 10.1016/j.expneurol.2018.10.013. Epub 2018 Oct 25.

Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood-Brain Interface. Lenz M, Eichler A, Vlachos A. Biomolecules. 2021 Feb 26;11(3):359. doi: 10.3390/biom11030359.