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: 9980516
• 负责人: Ukpong Bassey Eyo
• 金额: $ 23.97万
• 依托单位: UNIVERSITY OF VIRGINIA
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980516
• 关键词: Address; Apoptotic; Biology; Blood - brain barrier anatomy; Brain; Cell physiology; Cells; Chemotaxis; Childhood; Data; Development; Developmental Delay Disorders; Developmental Process; Disease; Electroencephalogram; Epilepsy; Exhibits; Fetal Alcohol Syndrome; Future; Genes; Goals; Human; Imaging Techniques; K22 Award; Life; Link; Measurement; Mentors; Microglia; Modeling; Molecular; Mus; Neuroglia; Neurons; Outcome; Pain; Pathology; Patients; Peripheral; Phagocytosis; Phase; Phenotype; Physiological; Physiology; Research; Resolution; Role; Seizures; Signal Transduction; Structure; Synapses; Synaptic plasticity; Syndrome; Technical Expertise; Techniques; Testing; Therapeutic; angiogenesis; autism spectrum disorder; brain cell; career; density; dravet syndrome; implantation; in vivo two-photon imaging; ischemic injury; macrophage; mouse model; neuronal excitability; neuronal survival; novel strategies; novel therapeutics; postnatal; postnatal development; postnatal period; programs; receptor; receptor function; synaptic pruning; transcriptome; translational study; two-photon

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

项目成果

A decade of diverse microglial-neuronal physical interactions in the brain (2008-2018).

大脑中不同小胶质细胞-神经元物理相互作用的十年（2008-2018）。

• DOI: 10.1016/j.neulet.2019.01.001
• 发表时间: 2019
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Uweru,JosephO;Eyo,UkpongB
• 通讯作者: Eyo,UkpongB