Abstracts

Rationale: Microglia, the brain’s resident immune cells, become activated in response to the brain injury caused by seizures. Microglia has been implicated in other neurological disorders because they phagocytize debris and release proinflammatory factors that can lead to more neuronal death. P2RY12 is a microglial-specific protein that is important for activation of microglia. Studies suggest that seizure phenotypes worsen with the genetic deletion of P2RY12. The mechanism of how microglial P2RY12 reduces seizure severity has yet to be understood. The objective of our research is to investigate the different mechanisms that could be underlying the P2Y12R role in seizures.

Methods: In our present study we performed Kainic acid (KA) induced seizures on mice with microglia eliminated  by PLX with or without P2RY12 gene knocked out (and appropriate controls). We then assessed the cytokine expression levels with a cytokine assay, assessed perineuronal net levels using WFA staining and imaging, and assessed microglial surveillance using live imaging.

Results: We found that microglia elimination or P2RY12 depletion did not change cytokine expression with seizures and perineuronal nets did not change with microglial depletion or in P2RY12KOs. However, the average surveillance index of microglia during chemo-convulsion was decreased in P2RY12KOs.

Conclusions: These results suggest that microglial P2RY12 could play a role in reducing seizure severity by increasing microglial surveillance during seizures.

Funding: Please list any funding that was received in support of this abstract.: NIH R01. Project Number: R01NS119243.