Microglial P2Y12 Receptors in Normal Developmental Physiology and Seizures

正常发育生理学和癫痫发作中的小胶质细胞 P2Y12 受体

• 批准号: 9608624
• 负责人: Ukpong Bassey Eyo
• 金额: $ 9.34万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-08 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9608624
• 关键词: Microglial; P2Y12; Receptors; Normal; Developmental

The overall goal of the proposed research for this K22 award is to test the hypothesis that P2Y12 receptors regulate prime microglial cell function during normal development and contribute to physiological neuronal excitability and consequently outcomes from a developmental seizure disorder. In the mentored Phase I, I will develop technical skill in (i) high resolution two photon in vivo imaging techniques in and (ii) electroencephalogram (EEG) implantation seizure measurement in developing mice. Having developed these techniques, in the independent Phase II, I will address the specific aims of this proposal including determining the role of P2Y12 receptors in microglial colonization and phagocytosis in the developing brain (Aim 1); determining the role of microglial P2Y12 receptors in synaptic structure and function (Aim 2); and determining any contributions of microglial P2Y12 receptors in the seizure phenotypes and outcomes in a developmental seizure model of Dravet Syndrome. When completed, this proposal will provide an understanding of P2Y12 receptor roles in microglial activities and its consequences on neuronal maturation and seizure phenotypes that could inform future therapeutic approaches.

本项K22奖研究的总体目标是验证以下假设