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.

Public Health Relevance

This study investigates which IL-1R1 expressing cell type (s) mediate IL-1 induced behavior changes. We will create a genetic model in which IL-1R1 expression will be restricted to the cell type of interest to dissect the role of cell type specifi IL-1R1 mediated effects. This model will be broadly useful for numerous studies on the cellular mechanisms of IL-1 related behavior disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH099482-02
Application #
8598110
Study Section
Clinical Neuroimmunology and Brain Tumors Study Section (CNBT)
Program Officer
Desmond, Nancy L
Project Start
2012-12-15
Project End
2014-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
2
Fiscal Year
2014
Total Cost
$172,921
Indirect Cost
$60,421
Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Liu, Xiaoyu; Nemeth, Daniel P; Tarr, Andrew J et al. (2016) Euflammation attenuates peripheral inflammation-induced neuroinflammation and mitigates immune-to-brain signaling. Brain Behav Immun 54:140-8
Liu, Xiaoyu; Yamashita, Tetsuji; Chen, Qun et al. (2015) Interleukin 1 type 1 receptor restore: a genetic mouse model for studying interleukin 1 receptor-mediated effects in specific cell types. J Neurosci 35:2860-70
Liu, Xiaoyu; Quan, Ning (2015) Immune Cell Isolation from Mouse Femur Bone Marrow. Bio Protoc 5: