[en] The highest risk factor for the development of neurodegenerative diseases like tauopathies is aging. Many physiological decrements underlying aging are linked to cellular senescence. Senescent cells are characterized by an irreversible growth arrest and formation of a senescence-associated secretory phenotype (SASP), a proinflammatory secretome that modifies the cellular microenvironment and contributes to tissue deterioration. Microglia, the innate immune cells in the brain, can enter a senescent state during aging. In addition, senescent microglia have been identified in the brains of tau-transgenic mice and patients suffering from tauopathies. While the contribution of senescent microglia to the development of tauopathies and other neurodegenerative diseases is a growing area of research, the effect of tau on microglial senescence remains elusive. Here, we exposed primary microglia to 5 and 15 nanomolar (nM) of monomeric tau for 18 h, followed by a recovery period of 48 h. Using multiple senescence markers, we found that exposure to 15 nM, but not 5 nM of tau increased levels of cell cycle arrest and a DNA damage marker, induced loss of the nuclear envelope protein lamin B1 and the histone marker H3K9me3, impaired tau clearance and migration, altered the cell morphology and resulted in formation of a SASP. Taken together, we show that exposure to tau can lead to microglial senescence. As senescent cells were shown to negatively impact tau pathologies, this suggests the presence of a vicious circle, which should be further investigated in the future.
Precision for document type :
Review article
Disciplines :
Neurology Immunology & infectious disease Life sciences: Multidisciplinary, general & others
Author, co-author :
Karabag, Deniz; Department for Neuroimmunology, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Faculty of Medicine and University Hospital Cologne, Cluster of Excellence Cellular Stress Response in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
Scheiblich, Hannah; Department for Neuroimmunology, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Griep, Angelika; Department for Neuroimmunology, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Santarelli, Francesco; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Schwartz, Stephanie; Department for Neuroimmunology, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) ; Department for Neuroimmunology, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Divison of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Ising, Christina ; Faculty of Medicine and University Hospital Cologne, Cluster of Excellence Cellular Stress Response in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
External co-authors :
yes
Language :
English
Title :
Characterizing microglial senescence: Tau as a key player.
This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2030—390661388 and—EXC 2151—390873048. We would like to thank the Light Microscope Facility at German Center for Neurodegenerative Diseases (DZNE) in Bonn for the microscope and analysis software. Open Access funding enabled and organized by Projekt DEAL.This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2030—390661388 and—EXC 2151—390873048. We would like to thank the Light Microscope Facility at German Center for Neurodegenerative Diseases (DZNE) in Bonn for the microscope and analysis software. Open Access funding enabled and organized by Projekt DEAL.
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