Microglial P2RY12 Play a Role in Reducing Seizure Severity
Abstract number :
1.423
Submission category :
1. Basic Mechanisms / 1F. Other
Year :
2022
Submission ID :
2233018
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:29 AM
Authors :
Bridley Jenkins, B.A., Psychology, May 2023 – University of Virginia School of Medicine; Ukpong Eyo, PhD – Assistant Professor, Center for Immunology and Glia, Neuroscience, University of Virginia School of Medicine; Synphane Gibbs, B.S., M.S. – PhD Candidate, Pharmacology, University of Virginia School of Medicine
Rationale: Dravet syndrome is a rare and severe pediatric genetic epilepsy characterized by febrile seizures, and drug-resistant epilepsy that begins in the first year of life. With Dravet patients continuing to suffer from highly drug-resistant seizures, it is important that we continue working to find proper and effective solutions. One possible solution could come from understanding the novel relationship between P2RY12, a microglial receptor responsible for triggering microglia’s processes to move to sites of injury in the brain, and seizures. The aim of this study was to determine whether the microglial P2RY12 receptor plays a role in seizure severity in wild type mice and Dravet Syndrome, SCN1A +/-, mice models.
Methods: To determine the relationship between microglial P2RY12 and seizures, we compared the average kainic-acid induced seizure scores using the Racine Seizure Scoring Scale between mice with their microglial P2RY12 receptor and P2RY12KO mice. To determine the relationship between microglial P2RY12 and seizures in our Dravet mice, we compared the heat plate-induced febrile seizures, specifically the onset of first seizure and time of death differences, between SCN1A+/- mice and SCN1A+/-:P2RY12-/- mice.
Results: We found that the P2RY12KO mice both over time and on average had higher Racine seizure scores compared to the mice with P2RY12 in KA-induced seizures. The SCN1A+/-:P2RY12-/- mice also, on average, had an earlier onset of febrile seizures and earlier times of death compared to the SCN1A+/- mice.
Conclusions: Therefore, the microglial P2RY12 receptor may play a role in reducing the seizure severity of SCN1A +/- Dravet Syndrome mice.
Funding: American Epilepsy Society
Basic Mechanisms