Effects of SARS-CoV-2 infection and immunity on hippocampal function

• Applicants: Professor Dr. Luka Cicin-Sain; Professor Dr. Martin Korte
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539506671

Clinical studies have documented COVID-19 convalescents experiencing a wide range of neurological symptoms after recovery, including persistent cognitive impairment. Cognitive decline following viral infection may be caused by direct damage to the brain by the virus or due to the immune response to a pronounced infection. Since aging affects the immune system at the cellular and molecular levels, the elderly are particularly affected by SARS-CoV-2 infection and are at increased risk of severe COVID-19 disease. Moreover, the aged brain is more sensitive to inflammatory stimuli, leading to more severe and long-term impairments in brain function. It is still unclear whether the increased activation of the immune response in the periphery or in the central nervous system (CNS) upon SARS-CoV-2 infection leads to chronic neuroinflammation and subsequent neuronal dysfunction. In this project, we aim to investigate the detailed mechanisms of the long-term effects of SARS-CoV-2 infection on the CNS and the possible influence of aging. There is growing evidence of a link between frequent infections and dementia risk, because inflammation and oxidative stress are key features of many neurodegenerative diseases. While it is known that SARS-CoV-2 strongly triggers the immune system, the effects of SARS-CoV-2 infection on the onset and progression of neurodegeneration remain elusive. Therefore, using previously established mouse models of Alzheimer's disease (AD) and infection, we are particularly interested in deciphering the potential impact of SARS-CoV-2 infection on the onset and progression of AD. Our collaboration brings together interdisciplinary expertise in neurodegeneration, immunology and virology. Thus, we will use well-established methods and a unique technological infrastructure to study COVID-19 in relevant mouse models of infection and neurodegeneration. In addition, we plan to investigate the effects of vaccination as potential preventive strategies against the neurological long-COVID consequences of SARS-CoV-2 infection, particularly in vulnerable individuals.

• DFG Programme: Research Grants