Biology subjects

Korte, M.

Publications and source records attributed to Korte, M..

4 recordsLinked to original sources

bioRxiv2025

Glial cells promote infection by neurotropic Influenza A viruses in vitro

Although influenza A viruses (IAV) are notorious respiratory pathogens, some IAV strains can reach and replicate in the central nervous system (CNS) in vivo. In particular, highly pathogenic avian influenza viruses (HPAIV) pose a threat for future pandemics and are linked to greater neurotropic potential. Moreover, neurotropic IAV strains have shown a more significant impact on the onset and pathogenesis of neurodegenerative diseases (NDD). However, despite its clinical relevance, the dynamics and cellular tropism of IAV infection in the CNS are not well understood. In this study, we analyzed the replication of HPAIV H7N7 in vitro using a primary murine triple co-culture system comprising neurons, astrocytes, and microglia. We found that microglia become highly infected early on and induce a strong pro-inflammatory response before undergoing apoptosis. Using fluorescence microscopy with automated single-cell profiling, we found that, in contrast to non-neurotropic H3N2, the H7N7 nucleoprotein accumulated in neuronal somata throughout the infection without being transported into dendrites or axons. A combination of single-cell and co-culture replication assays led us to conclude that astrocytes are the primary virus producers of HPAIV H7N7 in the CNS. Our results illuminate the acute phase of neurotropic IAV infection, highlighting its implications for the association between IAV and the development of neurodegenerative diseases.

microbiology↗

bioRxiv2021

IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer s disease mouse model

The anti-inflammatory cytokine interleukin-37 (IL-37) is a member of the IL-1 family but not expressed in mice. We used a human IL-37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Those studies demonstrate an immune-modulatory role of IL-37 which can be characterized as an important suppressor of innate immunity. We investigated the functions of IL-37 in the CNS and explored the effects of IL-37 on neuronal architecture and function, microglia phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. Reduced spine density, activated microglia phenotype and impaired long-term potentiation (LTP) were observed in wild-type mice after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimers disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent the loss of cognitive abilities in a mouse model of AD.

neuroscience↗

bioRxiv2021

Influenza A virus (H1N1) infection induces microglia activation and temporal dysbalance in glutamatergic synaptic transmission.

3.Influenza A virus (IAV) causes respiratory tract disease and is responsible for seasonal and reoccurring epidemics affecting all age groups. Next to typical disease symptoms such as fever and fatigue, IAV infection has been associated with behavioral alterations presumably contributing to the development of major depression. Previous experiments using IAV/H1N1 infection models have shown impaired hippocampal neuronal morphology and cognitive abilities, but the underlying pathways have not been fully described. In this study, we demonstrate that infection with a low dose non-neurotrophic H1N1 strain of IAV causes ample peripheral immune response followed by a temporary blood-brain-barrier disturbance. Although histological examination did not reveal obvious pathological processes in the brains of IAV-infected mice, detailed multidimensional flow cytometric characterization of immune cells uncovered subtle alterations in the activation status of microglia cells. More specifically, we detected an altered expression pattern of major histocompatibility complex class I and II, CD80, and F4/80 accompanied by elevated mRNA levels of CD36, CD68, C1QA, and C3, suggesting evolved synaptic pruning. To closer evaluate how these profound changes affect synaptic balance, we established a highly sensitive multiplex flow cytometry-based approach called Flow Synaptometry. The introduction of this novel technique enabled us to simultaneously quantify the abundance of pre- and postsynapses from distinct brain regions. Our data reveal a significant reduction of VGLUT1 in excitatory presynaptic terminals in the Cortex and Hippocampus, identifying a subtle dysbalance in glutamatergic synapse transmission upon H1N1 infection in mice. In conclusion, our results highlight the consequences of systemic IAV-triggered inflammation on the central nervous system and the induction and progression of neuronal alterations.

immunology↗

bioRxiv2018

Neuroligins mediate presynaptic maturation through brain-derived neurotrophic factor signaling

Maturation is a process that allows synapses to acquire full functionality; failures in synaptic maturation may contribute to neurodevelopmental disorders. Neuroligins are postsynaptic cell-adhesion molecules essential for synapse maturation, but the underlying pathways are incompletely understood. Here, we show that maturational increases in active zone stability and synaptic vesicle recycling rely on the joint action of Neuroligins and brain-derived neurotrophic factor (BDNF). Applying BDNF to neuronal cultures mimicked the maturation-promoting effects of overexpressing the Neuroligin isoforms NL1 or NL2. Inhibiting BDNF signaling reduced the effects of NL1 and NL2 on presynaptic maturation and of NL2 on synapse formation. Applying BDNF to NL1-knockout mouse cultures rescued defective presynaptic maturation, indicating that BDNF acts downstream of NL1 and can restore presynaptic maturation at late stages of network development. Our data introduce BDNF as a novel and essential component in a transsynaptic pathway linking Neuroligin-mediated cell adhesion, neurotrophin action and presynaptic maturation.

neuroscience↗