Journal Article

DZNE-2023-00739

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Characterizing microglial senescence: Tau as a key player.

Karabag, D. (First author)DZNE* ; Scheiblich, H.DZNE* ; Griep, A.DZNE* ; Santarelli, F.DZNE* ; Schwartz, S. ; Heneka, M. T.DZNE* ; Ising, C.

2023
Wiley-Blackwell Oxford

This record in other databases:    

Please use a persistent id in citations: doi:10.1111/jnc.15866

Abstract: 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.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Microglia (MeSH) ; Aging: genetics (MeSH) ; Cellular Senescence: physiology (MeSH) ; Tauopathies (MeSH) ; Biomarkers (MeSH) ; Mice, Transgenic (MeSH) ; DNA damage ; SASP ; aging ; cellular senescence ; microglia ; tau ; Biomarkers

---

Contributing Institute(s):

1. Neuroinflammation, Biomarker (AG Heneka 2 ; AG Heneka ; AG Heneka)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---