Mikayla Anton
Research Mentor(s): Thomas Sanderson
Mentor Department:
Authors:
Session: Session 2 (10:00am – 10:50am)
Presentation Type: Poster 8
Abstract
Microglia play a crucial role in the inflammatory response following ischemic stroke, activating in response to damage-associated molecular patterns (DAMPs) released from injured brain tissue. Detection of DAMPs trigger microglial polarization, leading to the activation of pro-inflammatory and anti-inflammatory phenotypes. Pro-inflammatory microglia contribute to the release and activation of cytokines such as IL-1B, TNFa, and IL-6 which drive neuroinflammation. Anti-Inflammatory microglia facilitate tissue repair through the clearance of debris. Autophagy, the process where cellular components are degraded and recycled, plays a critical role in the regulation of the microglial polarization, with its dysfunction linked to sustained neuroinflammation. This study investigates the impact of BzATP, a P2X7 receptor agonist, on microglial activation, respiration, and autophagy. Western blot analysis demonstrated increased expression of inflammatory markers (iNOS, NLRP3) following BzATP stimulation along with autophagy suppression, indicated by p62 accumulation and a reduced LC3-B/A ratio. To explore microglial respiration, we performed the Mito Stress Test, which revealed that BzATP-treated microglia exhibited increased maximal respiration following FCCP administration. However, live-cell imaging showed an acute decrease in mitochondrial membrane potential, indicating an overactivation of the electron transport chain and heightened metabolic activity. Additionally, inhibition of the mitochondrial calcium uniporter (MCU) via Ru360 attenuated the increase in maximal respiration brought on by BzATP. This suggests that mitochondrial calcium may be a key driver of metabolic and inflammatory responses in microglia. These findings suggest a link between autophagic suppression, mitochondrial calcium concentration, and inflammation, which can offer new insights into potential therapeutic interventions for stroke-induced neuroinflammation.
