Characterizing microglial senescence: Tau as a key player.

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Aging is the primary risk factor for neurodegenerative diseases such as tauopathies.
• Cellular senescence, characterized by irreversible growth arrest and a senescence-associated secretory phenotype (SASP), contributes to age-related tissue deterioration.
• Senescent microglia have been observed in aging brains and in tauopathy models, but the effect of tau on microglial senescence is unknown.

Purpose of the Study:

• To investigate the effect of monomeric tau exposure on primary microglia.
• To determine if tau can induce microglial senescence and its associated characteristics.

Main Methods:

• Primary microglia were exposed to 5 and 15 nanomolar (nM) of monomeric tau for 18 hours.
• A 48-hour recovery period was allowed post-exposure.
• Multiple senescence markers, including cell cycle arrest, DNA damage, lamin B1, H3K9me3, tau clearance, migration, cell morphology, and SASP formation, were analyzed.

Main Results:

• Exposure to 15 nM tau, but not 5 nM, significantly increased markers of cell cycle arrest and DNA damage.
• Tau exposure led to loss of lamin B1 and H3K9me3, impaired tau clearance and migration, and altered cell morphology.
• A senescence-associated secretory phenotype (SASP) was observed in tau-exposed microglia.

Conclusions:

• Monomeric tau can induce senescence in primary microglia.
• This microglial senescence is associated with impaired cellular functions and the release of inflammatory factors (SASP).
• The findings suggest a potential self-perpetuating cycle where tau pathology induces microglial senescence, which in turn may exacerbate tau pathology, warranting further investigation.