Microglial activation induced by the alarmin S100B is regulated by poly(ADP-ribose) polymerase-1

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Brain injury triggers microglial activation via proinflammatory mediators.
• Alarmins, signaling molecules from damaged cells, contribute to microglial activation.
• Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in regulating microglial responses to brain injury.

Purpose of the Study:

• To investigate the role of PARP-1 in mediating the signaling effects of the alarmin S100B on microglial activation.
• To determine if PARP-1 inhibition can attenuate S100B-induced microglial responses.

Main Methods:

• Primary microglial cultures were treated with exogenous S100B.
• PARP-1 deficient (PARP-1(-/-)) microglia and wild-type microglia treated with the PARP inhibitor veliparib were used.
• S100B was injected directly into the brain of wild-type mice with or without PARP-1 inhibition.
• Microglial morphology, gene expression (IL-1β, TNFα, iNOS), and release of matrix metalloproteinase 9 and nitric oxide were assessed.

Main Results:

• Exogenous S100B induced microglial activation, characterized by morphological changes and upregulation of inflammatory genes and mediators.
• Most S100B-induced effects were attenuated in PARP-1(-/-) microglia and in wild-type microglia treated with veliparib.
• In vivo PARP-1 inhibition significantly reduced S100B-induced microglial activation and gene expression changes in the injured brain.

Conclusions:

• PARP-1 plays a significant role in regulating S100B-mediated microglial activation.
• PARP-1 inhibition demonstrates potential anti-inflammatory effects in acutely injured brain, partly through modulation of S100B signaling pathways.