Source Paper
β-Adrenergic Receptor Antagonism Prevents Anxiety-Like Behavior and Microglial Reactivity Induced by Repeated Social Defeat
Eric S. Wohleb, et al.
Source Paper
Eric S. Wohleb, et al.
Journal of Neuroscience • 2011
Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b + /CD45 high /Ly6C high macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.
Objective: Assessment of social defeat responses in IL-1 receptor type-1-deficient mice to evaluate IL-1 signaling in stress-induced anxiety and microglia activation
This is a IL-1 Receptor Knockout Study protocol using mouse as the model organism. The procedure involves 9 procedural steps, 2 equipment items, 2 materials. Extracted from a 2011 paper published in Journal of Neuroscience.
Model and subjects
mouse • IL-1 receptor type-1-deficient mice and wild-type controls • Not specified • Not specified • Not specified • Not specified
Study window
Estimated timing pending
Core workflow
Repeated Social Defeat Stress • Assessment of Anxiety-Like Behavior • c-Fos Staining Analysis
Primary readouts
Key equipment and reagents
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Mice were subjected to repeated social defeat stress paradigm
Note: Study examined both wild-type and IL-1 receptor type-1-deficient mice
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Anxiety-like behavior was measured in mice following social defeat stress
Note: Anxiety-like behavior was dependent on β-adrenergic and IL-1 receptor activation
“Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain”
Brain tissue was analyzed for c-Fos staining in regions associated with fear and threat appraisal
Note: c-Fos activation was increased in IL-1 receptor type-1-deficient mice but did not promote anxiety-like behavior
“Repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior”
Flow cytometry analysis of inflammatory markers on microglia and macrophages including CD14, CD86, and TLR4
Note: Markers were increased on microglia and macrophages after social defeat
“Several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat”
Analysis of microglia morphology in medial amygdala, prefrontal cortex, and hippocampus
Note: Deramified microglia were increased in these brain regions following social defeat
“Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus”
mRNA expression analysis of microglia for IL-1β and glucocorticoid responsive genes (GILZ and FKBP51)
Note: Social defeat increased IL-1β and reduced glucocorticoid responsive genes
“mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes”
Microglia isolated from socially defeated and control mice were cultured and stimulated with lipopolysaccharide
Note: Microglia from defeated mice produced higher levels of IL-6, TNF-α, and MCP-1
“Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide”
β-adrenergic receptor antagonist propranolol was administered to prevent stress-dependent changes
Note: Propranolol prevented stress-dependent changes in microglia and macrophages
“The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist”
Comparison of behavioral and immunological responses between IL-1 receptor type-1-deficient mice and wild-type controls
Note: IL-1 receptor type-1 deficiency prevented anxiety-like behavior and microglia activation despite increased c-Fos
“Repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Assessment of social defeat responses in IL-1 receptor type-1-deficient mice to evaluate IL-1 signaling in stress-induced anxiety and microglia activation
Objective
Assessment of social defeat responses in IL-1 receptor type-1-deficient mice to evaluate IL-1 signaling in stress-induced anxiety and microglia activation
Subjects
From papermouse • IL-1 receptor type-1-deficient mice and wild-type controls • Not specified • Not specified • Not specified
Sample count
From paperNot specified
Cohort notes
From paperStudy compared IL-1 receptor type-1-deficient mice with control mice
Repeated Social Defeat Stress (Not specified)
Assessment of Anxiety-Like Behavior (Not specified)
c-Fos Staining Analysis (Not specified)
Microglia and Macrophage Phenotyping (Not specified)
C-Fos staining in brain regions associated with fear and threat appraisal
From paperNot specified in the provided text
Artifact type
Representative image panels with region or marker comparisons
Comparison focus
Compare staining intensity, structure, or cell counts across matched conditions
Anxiety-like behavior
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
C-Fos staining in brain regions associated with fear and threat appraisal
From paperRaw artifact
Field or section images captured from matched samples
Processed artifact
Selected representative panels with quantified intensity, counts, or area measurements
Final reported form
Per-group imaging summaries with representative figures and quantified endpoints
Anxiety-like behavior
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified in the provided text
Scoring or quantification
Quantify the primary readouts for this experiment: C-Fos staining in brain regions associated with fear and threat appraisal; Anxiety-like behavior; CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain; Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for C-Fos staining in brain regions associated with fear and threat appraisal, Anxiety-like behavior, CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain, Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Source links and direct wording from the methods section for validation and deeper review.
Citation
Eric S. Wohleb et al. (2011). β-Adrenergic Receptor Antagonism Prevents Anxiety-Like Behavior and Microglial Reactivity Induced by Repeated Social Defeat. Journal of Neuroscience
Repeated Social Defeat Stress • Protocol step
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Assessment of Anxiety-Like Behavior • Protocol step
“Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain”
c-Fos Staining Analysis • Protocol step
“Repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior”
Microglia and Macrophage Phenotyping • Protocol step
“Several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat”
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