IL-1R1-restore: dissecting cellular mechanisms of IL-1-mediated behavior effects

IL-1R1-restore：剖析 IL-1 介导的行为效应的细胞机制

• 批准号: 8598110
• 负责人: Ning Quan
• 金额: $ 19.21万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-15 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598110
• 关键词: Address; Affect; Animal Model; Anxiety; Astrocytes; Behavior; Behavioral; Brain; Cells; Detection; Endothelial Cells; Fluorescence; Gene Expression; Genetic; Genetic Models; Grant; Hippocampus (Brain); Hypothalamic structure; Immune; Impairment; Interleukin-1; Interleukin-1 Receptors; Learning; Lifestyle-related condition; Literature; MAPK14 gene; Major Depressive Disorder; Maps; Mediating; Memory; Messenger RNA; Methods; Microglia; Modeling; Monitor; Mus; NF-kappa B; Neuroglia; Neurons; Pattern; Physiological; Play; Proteins; Reporting; Role; Sick Role; Signal Pathway; Signal Transduction; behavior change; brain cell; cell type; interest; mouse model; neural circuit; novel; promoter; public health relevance; selective expression

DESCRIPTION (provided by applicant): It is well known actions of interleukin-1 (IL-1) in the brain contributes to numerous behavior abnormalities, including illness behavior, heightened anxiety, major depression, and impairment in learning and memory. However, cellular mechanisms by which IL-1 affects neurons involved in these behaviors are unclear. In this exploratory grant, we will create a novel genetic mouse model that selectively expresses IL-1R1 on a defined cell type. In this mouse model, we can restrict cell type specific expression of IL-1R1 under its native promoters, thus permitting analysis of IL-1-mediated effects in mice which express IL-1R1 at physiological levels only in the cell type(s) of interest. Additional advantages of this model are IL-1R1 gene expression at mRNA level is able to be monitored by a knockin red fluorescence and detection of IL-1R1 protein will be facilitated by a 3HA tag added to the C-terminus of the IL-1R1 protein. We will use this model to determine the role cell type-specific IL- 1R1 expression plays in both illness behavior and spatial learning/memory following immune stimulation.

描述（由申请人提供）：这是白介素-1（IL-1）在大脑中的众所周知的作用，导致许多行为异常，包括疾病行为，焦虑症，重度抑郁，学习和记忆中的障碍。但是，IL-1影响这些行为涉及的神经元的细胞机制尚不清楚。在此探索性授予中，我们将创建一个新型的遗传小鼠模型，该模型在定义的细胞类型上有选择地表达IL-1R1。在该小鼠模型中，我们可以限制IL-1R1在其天然启动子下的细胞类型特异性表达，从而允许对仅在感兴趣的细胞类型中以生理水平表达IL-1R1的IL-1介导的效应。该模型的其他优势是在mRNA水平下的IL-1R1基因表达能够通过敲击红荧光来监测，IL-1R1蛋白的检测将通过添加到IL-1R1蛋白的C端的3HA标签来促进IL-1R1蛋白的检测。我们将使用此模型来确定细胞类型特异性IL- 1R1表达在免疫刺激后在疾病行为和空间学习/记忆中发挥作用。

项目成果

Immune Cell Isolation from Mouse Femur Bone Marrow.

从小鼠股骨骨髓中分离免疫细胞。

• DOI: 10.21769/bioprotoc.1631
• 发表时间: 2015
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Liu,Xiaoyu;Quan,Ning
• 通讯作者: Quan,Ning

Networking into neural plasticity: a rising score on the cytokine learning curve.

神经可塑性网络：细胞因子学习曲线上的得分不断上升。

• DOI: 10.1016/j.bbi.2013.06.008
• 发表时间: 2013
• 期刊: Brain, behavior, and immunity
• 作者: Quan,Ning